移植后血流感染相关研究及肾移植感染基因多态性研究
摘要
本研究分两部分,包括进行实体器官移植后血流感染休克及死亡的危险因素研究及进行肾移植术后感染基因多态性研究。第一部分通过回顾性分析98例实体器官移植受者发生的133次血流感染,评估可能导致受者发生感染性休克或死亡的危险因素,同时回顾性分析2002年1月至2012年1月间合并有血流感染的肝移植受者的死亡危险因素,以及分析本院在2008年1月至2010年4月间的21例进行肝或肾移植术并术后发生血流感染的受者的菌株以了解病原菌分布及其耐药性。
结果发现与实体器官移植受者合并血流感染时死亡率升高显著相关的危险因素为感染性休克和血小板计数<50,000/mm3;复数菌血流感染及早发型血流感染(移植术后第2周至第8周发生)是实体器官移植受者中感染性休克发生的独立危险因素；与肝移植合并血流感染的死亡率显著相关的危险因素包括升高的血清肌酐值及感染性休克；本院2008年1月至2010年4月间肝或肾移植术后发生血流感染中的病原菌以G-杆菌占优势,病原菌普遍对临床常用抗生素有较高耐药性。
第二部分了解IL-1β(-511C/T)与IL-1受体拮抗剂(86bp可变数量串联重复)基因多态性与肾移植术后一年内发生血流感染的相关性,并对TNFβ、IL-10、IL-1β和IL-1受体拮抗剂基因多态性能否预测肾移植术后一年内发生肺部感染进行调查,并结合其他影响因素评价甘露糖结合凝集素-2及纤维胶凝蛋白-2基因多态性与肾移植术后发生血流感染的相关性。
结果发现肾移植受者IL-1β-511CC基因型及IL-1β-511C的等位基因与肾移植术后一年内发生血流感染具相关性；受者TNFβ基因多态性是肺部感染的独立危险因素；受者甘露糖结合凝集素-2基因的5’非翻译区QQ+PQ基因型与血流感染的发生相关,FCN2外显子8区Thr236Met(+6359C>T)变异体是肾移植术后发生血流感染的独
第一部分实体器官移植后血流感染休克及死亡危险因素
第一章实体器官移植受者血流感染死亡危险因素
目的：寻找导致实体器官移植受者发生血流感染时导致死亡率增高的危险因素。
方法：回顾性分析98例实体器官移植受者发生的133次血流感染,评估可能的导致受者死亡的危险因素。依靠单因素分析和logistic回归方法来确立导致血流感染相关死亡的危险因素。
结果：入组受者平均年龄为42.3(42.3±12.8)岁。受者中绝大多数是院内获得性感染(79.6%),血流感染导致的死亡率为39.8%(39/98)。单因素分析显示腹腔内/胆道感染(P=0.011)、复数菌感染(P<0.001)、肝移植(P=0.002)、血小板计数<50,000/mm3(P<0.001)、淋巴细胞计数<300/mm3(P=0.027)及感染性休克(P<0.001)等变量在死亡组及存活组中存在显著差别。logistic回归分析显示感染性休克和血小板计数<50,000/mm3是导致实体器官移植血流感染相关死亡的独立危险因素。
结论：与实体器官移植受者合并血流感染时死亡率升高显著相关的危险因素为感染性休克和血小板计数<50,000/mm3。选择了恰当的抗生素进行治疗的受者中血流感染导致的死亡率依然相当高,实施恰当的措施以预防实体器官移植受者血流感染的发生提高受者生存率较治疗本身更为重要和可靠。
第二章实体器官移植受者血流感染并感染性休克危险因素
目的：调查实体器官移植受者发生血流感染同时合并感染性休克的危险因素。
方法：回顾性调查98例实体器官移植受者包括进行肾、心脏、胰肾联合、肝肾联合或者原位肝移植的临床资料。根据美国疾病控制中心制定的相应标准,对98例实体器官移植受者合并血流感染时所有有意义的变量进行单因素及1ogistic回归分析。
结果：该98例实体器官移植受者共发生133次血流感染。39例受者发生感染性休克(39/98),其中31例受者(79%)死亡。98例血流感染受者中,革兰氏阴性菌占38.5%,革兰氏阳性菌占15.4%,真菌占2.6%以及复数菌占43.5%。肺部来源占41.8%,是本研究血流感染病原体中最常见的来源部位。腹腔内/胆道来源紧随其后,占24.5%。单因素分析中,术后第2周至第8周发生的血流感染(P0.014)、复数菌血流感染(P=0.001)、腹腔内/胆道部位来源(P=0.011)和肝移植(P=0.002)在休克组及非休克组中存在显著性差异。logistic回归分析中,只有复数菌血流感染和术后第2周至第8周发生的血流感染能够独立预测实体器官移植合并血流感染的受者中感染性休克的发生。
结论：复数菌血流感染及早发型血流感染(移植术后第2周至第8周发生)是实体器官移植受者中感染性休克发生的独立危险因素。
第三章肝移植受者血流感染死亡危险因素分析
目的：目前关于合并血流感染的肝移植受者的死亡危险因素的研究非常缺乏。本研究回顾性分析2002年1月至2012年1月间合并有血流感染的肝移植受者的死亡危险因素。
方法：本回顾性研究期间,我院共实施135例肝移植,其中43例受者发生了77次血流感染。本研究使用单变量分析和多元逻辑回归以确定合并血流感染的肝移植的死亡危险因素。
结果：43例受者发生了血流感染(31-9%)。入选受者平均年龄45.1(45.1±14.1)岁。绝大多数为院内获得性感染(97.7%),超过半数的感染为复数菌感染(53.5%),24例发生死亡(55.8%)。单变量分析显示肝移植后血流感染相关死亡的危险因素为：腹腔内/胆道来源(P=0.011),复数菌感染(P=0.029),血小板计数<50,000/mm3(P=0.02),血肌酐值>1.5mg/dL (P=0.008),感染性休克(P<0.001)。多元逻辑回归分析显示血肌酐值>1.5mg/dL和感染性休克是肝移植后血流感染相关死亡的独立危险因素。
结论：与肝移植合并血流感染的死亡率显著相关的危险因素包括升高的血清肌酐值及感染性休克。因此有效预防肝移植受者血流感染的发生以及保护肾功能均十分重要。
第四章21例肝或肾移植术后血流感染病原菌分布及耐药性
目的：分析病原菌在肝或肾移植术后发生的血流感染中的分布情况及其耐药性特征,以期指导临床对抗生素进行合理使用。
方法：分析本院在2008年1月至2010年4月间的21例进行肝或肾移植术并术后发生血流感染的受者,21例血流感染的受者中共检出菌株24株,使用BD微生物鉴定系统进行药敏试验以了解病原菌分布及其耐药性。
结果：病原菌构成中包括占62.5%的G-杆菌及占37.5%的G+球菌。G-杆菌最敏感药物为喹诺酮(如环丙沙星)及碳青霉烯类(如美罗培南)抗生素。磺胺类及单环β内酰胺类(如氨曲南)抗生素耐药性最高,头孢类第一、二、三代抗生素(如头孢他啶)为其次；G+球菌最敏感药物的为糖肽类(如万古霉素)及恶唑烷酮类(如利奈唑胺)抗生素。
结论：本院2008年1月至2010年4月间肝或肾移植术后发生的血流感染中的病原菌以G-杆菌占优势,病原菌普遍对临床常用抗生素有较高的耐药性。
第二部分肾移植术后感染基因多态性研究
第一章IL-1家族基因多态性与肾移植后血流感染相关性
目的：血流感染在肾移植术后发病率及死亡率均高,目前暂无研究对IL-1家族基因多态性与肾移植术后血流感染发生敏感性的相关性进行调查。当前的研究因此对此进行调查以了解IL-1β(-511C/T)与IL-1受体拮抗剂(86bp可变数量串联重复)基因多态性与肾移植术后一年内发生的血流感染的相关性。
方法：选取21例术后一年内发生血流感染的肾移植受者作为调查对象及60例术后未发生感染的肾移植受者进行对照,自该81例肾移植受者的外周血白细胞以血液基因小量提取试剂盒提取全基因组DNA备用。包含AvaI酶切位点的区域通过PCR方法被扩增,该酶切位点位于IL-1β基因的-511位点处,扩增产物接着被限制性内切酶AvaⅠ消化。包含IL-1受体拮抗剂基因的86碱基对可变数量串联重复多态区域也通过PCR方法进行扩增。
结果：本研究发现单因素分析显示IL-1β-511CC基因型及IL-1β-511C等位基因在肾移植术后发生血流感染的受者中具有更高携带率(P值分别为0.023和0.015),未发现IL-1受体拮抗剂基因型和等位基因与肾移植术后血流感染的相关性(P值分别为0.508和0.507)；多因素分析表明,进行混杂因素调整后,IL-1β-511CC基因型(OR=4.400,95%CI=1.517-12.759, P=0.006)及IL-1β-511C等位基因(OR=2.444,95%CI：1.172-5.100,P=0.015)能够作为肾移植术后一年内发生血流感染的独立危险因素。
结论：本研究提供了肾移植受者IL-1β-511CC基因型及IL-1β-511C的等位基因与肾移植术后一年内发生血流感染具有相关性的证据,该研究结果提示基因型数据有助于提供更为精确预测血流感染发生的可能并有助于采取更好的保护血流感染易感者的策略。
第二章TNFβ、IL-10和IL-1家族基因多态性与肾移植后肺部感染相关性
目的：肾移植术后肺部感染发病率及死亡率均较高,本研究因此对于TNFβ、IL-10、IL-1β和IL-1受体拮抗剂基因多态性能否预测肾移植术后一年内发生肺部感染进行调查。
方法：受试者由33位肾移植术后发生肺部感染的受者及63位肾移植术后未发生感染的受者组成。96位受者的全基因组DNA自外周血白细胞中提取,包含NcoI、 RsaI和AvaI多态性位点的区域通过PCR的方法扩增,该三个位点分别位于TNFβ基因的+252位点、IL-10基因的-592位点以及IL-1β基因-511位点处,扩增产物分别被限制性内切酶NcoI、RsaI和AvaI消化,包含IL-1受体拮抗剂基因的86碱基对可变数量串联重复多态区域通过PCR方法扩增。
结果：单因素分析发现受体IL-10, IL-1β和IL-1受体拮抗剂基因多态性与肾移植术后发生肺部感染无关(P值分别为0.589,0.940和0.286)；然而与GG基因型相比较,受者TNFβ+252AA+AG基因型与肾移植术后肺部感染的发生显著相关(P=0.006)。进行多因素分析,经排除年龄因素影响,受者TNFβ+252AA+AG基因型能够成为独立预测肾移植术后一年内发生肺部感染的独立危险因素(OR=5.366,95%CI=1.470-19.589,P=0.011)。
结论：本研究提示受者TNFβ基因多态性可能成为肺部感染的独立危险因素,因此能够明确哪些受者能够从减少免疫抑制剂并加强预防感染的措施中受益。
第三章甘露糖结合凝集素-2基因多态性影响肾移植后血流感染发生
目的：甘露糖结合凝集素属于C型凝集素,主要依靠结合多种微生物表面的碳水化合物结构发挥作用。甘露糖结合凝集素-2基因在启动子区及外显子1区的基因多态性与甘露糖结合凝集素血清浓度降低有关,因之与移植术后的感染发生相关。本研究对甘露糖结合凝集素-2的基因型变异体与肾移植术后一年内发生的血流感染的相关性进行分析。
方法：前瞻性研究分析81例肾移植术后受者。对血流感染事件进行前瞻性收集。共对6个甘露糖结合凝集素-2基因的功能性单核苷酸变异点通过基因测序方法进行分析。
结果：多因素分析仅仅发现当与PP基因型进行比较时,受者甘露糖结合凝集素-2基因的5’非翻译区QQ+PQ基因型与血流感染的发生相关(OR=3.677,95%可信区间(CI)=1.127-11.998, P=0.031),没有发现甘露糖结合凝集素-2基因的其他5个单核苷酸变异与肾移植术后血流感染的发生相关。
结论：受者甘露糖结合凝集素-2基因的5’非翻译区QQ+PQ基因型与肾移植术后的血流感染的发生相关。
第四章纤维胶凝蛋白-2基因多态性预测肾移植后血流感染
目的：纤维胶凝蛋白-2的结构和功能与甘露糖结合凝集素相似,能与微生物表面的N-乙酰氨基葡糖相互作用,纤维胶凝蛋白-2启动子区及外显子8区基因多态性与血清中纤维胶凝蛋白-2浓度差异相关,并与移植术后感染相关。本研究结合其他影响因素评价纤维胶凝蛋白-2基因多态性与肾移植术后发生血流感染的相关性。
方法：前瞻性研究分析81例肾移植术后受者。共对5个纤维胶凝蛋白-2基因的功能性单核苷酸变异点通过PCR方法扩增后进行基因测序分析。血流感染事件进行前瞻性收集。对纤维胶凝蛋白-2的变异体与肾移植术后一年内发生的血流感染的相关性进行分析。
结果：单因素分析发现纤维胶凝蛋白-2基因的启动子区-986G/A位点变异体及外显子8区Thr236Met (+6359C>T)变异体与血流感染的发生率增高相关(P值均为0.016)。多因素分析仅发现外显子8区Thr236Met (+6359C>T)变异体与血流感染的高发生率相关(OR=4.917,95%可信区间(CI)=1.229-19.667, P=0.024)。未发现纤维胶凝蛋白-2基因的其他3个单核甘酸变异与发生血流感染相关。
结论：外显子8区Thr236Met(+6359C>T)变异体是肾移植术后发生血流感染的独立危险因素。
The present study includes part1Mortality and septic shock predictors of bloodstream infections in solid organ transplantation recipients, and part2Association between gene polymorphisms and infection after kidney transplantation. In part1, a retrospective study of133episodes of BSIs documented in98SOT patients was conducted to assess potential predictors of septic shock and mortality, and a retrospective study of77episodes of BSIs were observed following43of liver transplantation to assess risk factors for mortality. To determine the distribution of pathogens and their characteristics of drug susceptibility of bloodstream infections after renal or hepatic transplantation. The predictors significantly associated with increased mortality in SOT recipients with BSIs included decreased platelet count and septic shock. The risk factors for developing septic shock in SOT with bloodstream infections were early-onset (the2nd-8th week post transplant) and polymicrobial etiology. The risk factors significantly associated with increased mortality in liver transplant recipients with BSIs are higher serum creatinine levels and septic shock. Though gram positive coccus played an important role, most infections were caused by gram negative bacteria of bloodstream infections after renal or hepatic transplantation. The antibiotic resistant rate for gram negative bacteria was very high as well as gram positive coccus.
In part2, the study was conducted to determine the influence of the polymorphisms of interleukin-10(IL-113)(-511C/T)and IL-1receptor antagonist gene (IL-1RN)(86-bpVNTR) on the susceptibility to bloodstream infections within the first year after kidney transplantation, and investigate whether or not the polymorphisms of TNF β, IL-10, IL-1β and IL-1receptor antagonist (IL-lra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation. MBL2and FCN2genotypic variants were also analyzed for association with the incidence of bloodstream infections within the first year after kidney transplantation.
The present work provides evidence that recipient IL-1β-511CC genotype or IL-1β-511C allele is associated with the susceptibility to bloodstream infections within the first year after kidney transplantation and that recipient TNF β gene polymorphism may be useful in predicting pneumonia. Recipient QQ+PQ genotypes of MBL25'-UTR+4and recipient Thr236Met (+6359C>T) variant of exon8of FCN2have significant impact on the risk of developing bloodstream infections after kidney transplantation. There are17figures,18tables and135references.
Part1Mortality and septic shock predictors of bloodstream infections in solid organ transplantation recipients
Chapter I Mortality predictors of bloodstream infections in solid organ transplantation recipients
Objective:To assess the possible predictors influencing survival among solid organ transplantation(SOT) recipients with bloodstream infections(B SIs).
Methods:A retrospective study of133episodes of BSIs documented in98patients was conducted to assess potential predictors of mortality. The predictors were identified by univariate and multivariate logistic regression analyses.
Results:The mean age for the98enrolled patients was42.3years(42.3±12.8years). The majority of infections were nosocomial (79.6%), and the BSIs-related mortality rate was39.8%(39of98patients). The univariate analysis identified the following variables as predictors of BSIs-related mortality:intra-abdominal/biliary focus(P=0.011), polymicrobial infectionCP<0.001), liver transplant(P=0.002), platelet count<50,000/mm3(P<0.001), Lymphocyte count<300/mm3(P=0.027), and septic shock(P<0.001). The multivariate logistic regression analysis identified platelet count<50,000/mm3and septic shock as independent predictors of mortality.
Conclusion:The predictors significantly associated with increased mortality in SOT recipients with BSIs included decreased platelet count and septic shock. Although appropriate antimicrobial therapy, the BSIs-related mortality was very high. Special attention should be paid to schedule optimal strategies for BSIs control practices in a transplantation setting.
Chapter Ⅱ The risk factors for septic shock in solid organ transplantation recipients with bloodstream infections
Objective:To evaluate the risk factors for septic shock among solid organ transplant recipients with bloodstream infections.
Methods:A retrospective study consists of98subjects who underwent a kidney, heart transplant, simultaneous kidney-pancreas, liver-kidney, or orthotopic liver transplantation. All episodes of bloodstream infections significant according to the CDC criteria were analyzed.
Results:133episodes of bloodstream infections occurred in98patients, with39of them developing septic shock. Among39septic shock patients, bloodstream infections were due to polymicrobial in43.5%, gram-negative bloodstream infections in38.5%, gram-positive bloodstream infections in15.4%, and fungal in2.6%of patients. The lung was the most frequent source of bloodstream infections (41.8%), followed by intra-abdominal/biliary focus (24.5%). Empiric therapy was correct in72%of cases with shock. However,31(79%) patients died despite that20patients were adequate empiric antibiotic therapy. Risk factors for developing septic shock were the2nd to8th week post transplant (P=0.014), polymicrobial etiology (P=0.001), intra-abdominal/biliary focus (P=0.011), and liver transplant (P=0.002) Only the2nd to8th week post transplant and polymicrobial etiology were significant in multivariate analysis.
Conclusions:Our study revealed that risk factors for developing septic shock in SOT with bloodstream infections were early-onset (the2nd-8th week post transplant) and polymicrobial etiology.
Chapter III The Risk Factors for Mortality in Deceased Donor Liver Transplant Recipients with Bloodstream Infections
Objective:More data on the risk factors for mortality in liver transplant recipients with bloodstream infections (BSIs) are needed. From January2002to January2012, a retrospective analysis of BSIs in deceased donor liver transplant was reviewed.
Methods:During the retrospective study period,135deceased donor liver transplants were performed, and77episodes of BSIs were observed following43of them to assess risk factors for mortality. Risk factors were identified by univariate and multivariate logistic regression analysis.
Results:Forty-three of the recipients (31.9%) developed BSIs. The median age for these patients was45.1years(45.1±14.1years). The majority of infections were nosocomial (97.7%), and more than half were polymicrobial(53.5%). There were24deaths in these recipients (55.8%). The univariate analysis identified the following variables as the risk factors for BSIs-related mortality:Polymicrobial{P=0.029), platelet count<50,000/mm3(P=0.02), creatinine>1.5mg/dL (P=0.008), and septic shock(P<0.001). Multivariate logistic regression showed that the independent risk factors for mortality are creatinine>1.5mg/dL and septic shock.
Conclusion:The risk factors significantly associated with increased mortality in deceased donor liver transplant recipients with BSIs are higher serum creatinine levels and septic shock. Although appropriate antimicrobial treatment, BSIs accompanied by septic shock or higher serum creatinine levels are associated with high mortality rates. It is therefore essential to pay special attention to protection of renal function and effective control measures to reduce the incidence of BSIs.
Chapter IV Distribution of pathogen and resistance of BSIs after renal or hepatic transplantation:A clinical anylasis of21
Objective:To determine the distribution of pathogens and their characteristics of drug susceptibility of bloodstream infections after renal or hepatic transplantation, and to provide evidence for clinical anti-infection treatments.
Methods:Retrospective analysis to the pathogens and their drug susceptibility characteristics was carried out. These pathogens were isolated from the samples that came from patients with bloodstream infections after renal or hepatic transplantation from2008to2010.
Results:The main pathogens were gram negative bacteria (62.5%), and the next ones were gram positive bacteria (37.5%). The most common gram negative bacilli were Escherichia coli. While for gram positive bacteria, the main bacilli were Staphylococcus aureus. The gram negative bacteria were relatively sensitive to carbapenem and quinolone. The gram positive bacteria were sensitive to glycopeptides and oxazolidone.
Conclusions:Though gram positive coccus played an important role, most infections were caused by gram negative bacteria of bloodstream infections after renal or hepatic transplantation. The antibiotic resistant rate for gram negative bacteria was very high as well as gram positive coccus.
Part2Association between gene polymorphisms and infection after kidney transplantation
Chapter I Genetic association of interleukin-1βand its receptor antagonist gene polymorphisms with susceptibility to bloodstream infections in kidney transplant recipients
Objective:Bloodstream infections remain significant causes of morbidity and mortality after kidney transplantation. No study has investigated the association of IL-1cluster gene polymorphism with susceptibility to bloodstream infections in kidney transplant recipients so far. The present study was therefore, conducted to determine the influence of the polymorphisms of interleukin-1β (IL-1β)(-511C/T)and IL-1receptor antagonist gene (IL-1RN)(86-bpVNTR) on the susceptibility to bloodstream infections within the first year after kidney transplantation.
Methods:Subjects comprised21kidney transplant recipients with bloodstream infections and60noninfected kidney transplant recipients. Genomic DNA from these81kidney transplant recipients was extracted routinely from peripheral blood leukocytes. The region containing the Aval polymorphic site at position-511of IL-1β gene was amplified by polymerase chain reaction(PCR) and subsequently digested with AvaI restriction enzyme. The polymorphic regions within intron2of IL-1RN containing variable numbers of a tandem repeat (VNTR) of86base pairs were amplified by means of PCR.
Results:A higher presence of IL-1β-511CC genotype and IL-1β-511C allele in the recipients with bloodstream infections than in the noninfected recipients (P=0.023and P=0.015, respectively) was found. In contrast, the current study failed to show any significant difference, either in genotypic or allelic frequency for the IL-1RN polymorphism regarding the incidence of bloodstream infections (P=0.508and P=0.507, respectively). After adjusting, recipient IL-1β-511CC genotype (OR 4.400,95%CI=1.517-12.759, P=0.006) and recipient IL-1β-511C allele (OR=2.444,95%CI=1.172-5.100, P=0.015) predicted independently the risk for bloodstream infections within the first year after kidney transplantation.
Conclusion:The present work provides evidence that recipient IL-1β-511CC genotype or IL-1β-511C allele is associated with the susceptibility to bloodstream infections within the first year after kidney transplantation. These results suggest that genotyping data may allow more accurate prediction of bloodstream infections and the design of strategies to protect the most vulnerable patients.
Chapter Ⅱ Genetic association of tumor necrosis factor β, interleukin-10and interleukin-1gene cluster polymorphism with susceptibility to pneumonia in kidney transplant recipients
Objective:Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore, conducted to investigate whether or not the polymorphisms of TNF β, IL-10, IL-1β and IL-1receptor antagonist (IL-lra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation.
Methods:Subjects comprised33kidney transplant recipients with pneumonia and63non-infected kidney transplant recipients. Genomic DNA from these96kidney transplant recipients was extracted from peripheral blood leukocytes. The regions containing the Ncol polymorphic site at position+252of TNF β gene, the RsaI polymorphic site at position-592of IL-10gene and the Aval polymorphic site at position-511of IL-1β gene were amplified by polymerase chain reaction(PCR) and subsequently digested with Ncol, RsaI and Aval restriction enzyme, respectively. The polymorphic regions within intron2of IL-lra gene (IL-1RN) containing variable numbers of a tandem repeat (VNTR) of86base pairs, were amplified by PCR.
Results:Individual locus analysis showed that recipient IL-10, IL-1β and IL-1RN polymorphisms were not associated with the presence of pneumonia (P=0.589,0.940and0.286, respectively). However, compared with GG genotype, recipient TNF β+252AA+AG genotype was significantly associated with susceptibility to pneumonia (P=0.006). After adjusting for age of45years or older, recipient TNF β+252AA+AG (OR=5.366,95%confidence intervals (CI)=1.470-19.589, P0.011) independently predicted the risk for pneumonia within the first year after kidney transplantation.
Conclusion:These results suggested that recipient TNF β gene polymorphism may be useful in predicting pneumonia hence identifying individuals that could benefit from preventive treatment and a less potent immunosuppression regimen.
Chapter III Mannose-binding lectin gene polymorphisms influence the susceptibility to bloodstream infections in kidney transplant recipients
Objective:Mannose-binding lectin (MBL) is a C-type lectin that interacts with carbohydrate structures on microbial surfaces. Polymorphisms at the promoter and exon1of the MBL2gene are responsible for low serum levels of MBL and have been shown to play an important role in an increased risk of post-transplant infections. MBL2genotypic variants were analyzed for association with the incidence of bloodstream infections within the first year after kidney transplantation.
Methods:We prospectively analyzed81kidney transplant recipients. A total of6well-known functional Single-nucleotide polymorphisms(SNPs) in the MBL2gene of the recipients were determined by gene sequencing. The events of bloodstream infections were collected prospectively.
Results:Multivariate analyses only found an association of recipient QQ+PQ genotypes of MBL25'-UTR+4with the incidence of bloodstream infections (OR=3.677,95%confidence intervals (CI)=1.127-11.998, P=0.031) as compared to PP genotypes of MBL25'-UTR+4. No differences were found according to other5polymorphisms in the MBL2gene.
Conclusion:Recipient QQ+PQ genotypes of MBL25'-UTR+4have significant impact on the risk of developing bloodstream infections after kidney transplantation.
Chapter IV Gene polymorphisms of ficolin-2predict bloodstream infections risk after kidney transplantation
Objective:Ficolin-2interacts with N-acetylglucosamine on microbial surfaces and has similarities in structure and function to Mannose-binding lectin (MBL). Polymorphisms in the promoter region and exon8of the ficolin-2(FCN2) gene are responsible for differences in ficolin-2serum levels and have been shown to play an important role in an increased risk of post-transplant infections. We assessed the relationship between these polymorphic genes and bloodstream infections within the first year after kidney transplantation, in relation to major risk factors.
Methods:We prospectively analyzed81kidney transplant recipients. A total of5well-known functional Single-nucleotide polymorphisms(SNPs) in the FCN2gene of the recipients were determined by gene sequencing. Bloodstream infections events were collected prospectively. FCN2genotypic variants were analyzed for association with the incidence of bloodstream infections within the first year after kidney transplantation.
Results:Univariate analysis found-986G/A variant of promoter region(P=0.016) and Thr236Met (+6359OT) variant of exon8(P=0.016) are associated with the incidence of bloodstream infections. Multivariate analysis only found an association of recipient Thr236Met (+6359C>T) variant of exon8with the incidence of bloodstream infections (OR=4.917,95%confidence intervals (CI)=1.229-19.667, P=0.024). No differences were found according to other3polymorphisms in the FCN2gene.
Conclusion:Recipient Thr236Met (+6359C>T) variant of exon8are major determinants of the risk of developing bloodstream infections after kidney transplantation.
结果发现与实体器官移植受者合并血流感染时死亡率升高显著相关的危险因素为感染性休克和血小板计数<50,000/mm3;复数菌血流感染及早发型血流感染(移植术后第2周至第8周发生)是实体器官移植受者中感染性休克发生的独立危险因素；与肝移植合并血流感染的死亡率显著相关的危险因素包括升高的血清肌酐值及感染性休克；本院2008年1月至2010年4月间肝或肾移植术后发生血流感染中的病原菌以G-杆菌占优势,病原菌普遍对临床常用抗生素有较高耐药性。
第二部分了解IL-1β(-511C/T)与IL-1受体拮抗剂(86bp可变数量串联重复)基因多态性与肾移植术后一年内发生血流感染的相关性,并对TNFβ、IL-10、IL-1β和IL-1受体拮抗剂基因多态性能否预测肾移植术后一年内发生肺部感染进行调查,并结合其他影响因素评价甘露糖结合凝集素-2及纤维胶凝蛋白-2基因多态性与肾移植术后发生血流感染的相关性。
结果发现肾移植受者IL-1β-511CC基因型及IL-1β-511C的等位基因与肾移植术后一年内发生血流感染具相关性；受者TNFβ基因多态性是肺部感染的独立危险因素；受者甘露糖结合凝集素-2基因的5’非翻译区QQ+PQ基因型与血流感染的发生相关,FCN2外显子8区Thr236Met(+6359C>T)变异体是肾移植术后发生血流感染的独
第一部分实体器官移植后血流感染休克及死亡危险因素
第一章实体器官移植受者血流感染死亡危险因素
目的：寻找导致实体器官移植受者发生血流感染时导致死亡率增高的危险因素。
方法：回顾性分析98例实体器官移植受者发生的133次血流感染,评估可能的导致受者死亡的危险因素。依靠单因素分析和logistic回归方法来确立导致血流感染相关死亡的危险因素。
结果：入组受者平均年龄为42.3(42.3±12.8)岁。受者中绝大多数是院内获得性感染(79.6%),血流感染导致的死亡率为39.8%(39/98)。单因素分析显示腹腔内/胆道感染(P=0.011)、复数菌感染(P<0.001)、肝移植(P=0.002)、血小板计数<50,000/mm3(P<0.001)、淋巴细胞计数<300/mm3(P=0.027)及感染性休克(P<0.001)等变量在死亡组及存活组中存在显著差别。logistic回归分析显示感染性休克和血小板计数<50,000/mm3是导致实体器官移植血流感染相关死亡的独立危险因素。
结论：与实体器官移植受者合并血流感染时死亡率升高显著相关的危险因素为感染性休克和血小板计数<50,000/mm3。选择了恰当的抗生素进行治疗的受者中血流感染导致的死亡率依然相当高,实施恰当的措施以预防实体器官移植受者血流感染的发生提高受者生存率较治疗本身更为重要和可靠。
第二章实体器官移植受者血流感染并感染性休克危险因素
目的：调查实体器官移植受者发生血流感染同时合并感染性休克的危险因素。
方法：回顾性调查98例实体器官移植受者包括进行肾、心脏、胰肾联合、肝肾联合或者原位肝移植的临床资料。根据美国疾病控制中心制定的相应标准,对98例实体器官移植受者合并血流感染时所有有意义的变量进行单因素及1ogistic回归分析。
结果：该98例实体器官移植受者共发生133次血流感染。39例受者发生感染性休克(39/98),其中31例受者(79%)死亡。98例血流感染受者中,革兰氏阴性菌占38.5%,革兰氏阳性菌占15.4%,真菌占2.6%以及复数菌占43.5%。肺部来源占41.8%,是本研究血流感染病原体中最常见的来源部位。腹腔内/胆道来源紧随其后,占24.5%。单因素分析中,术后第2周至第8周发生的血流感染(P0.014)、复数菌血流感染(P=0.001)、腹腔内/胆道部位来源(P=0.011)和肝移植(P=0.002)在休克组及非休克组中存在显著性差异。logistic回归分析中,只有复数菌血流感染和术后第2周至第8周发生的血流感染能够独立预测实体器官移植合并血流感染的受者中感染性休克的发生。
结论：复数菌血流感染及早发型血流感染(移植术后第2周至第8周发生)是实体器官移植受者中感染性休克发生的独立危险因素。
第三章肝移植受者血流感染死亡危险因素分析
目的：目前关于合并血流感染的肝移植受者的死亡危险因素的研究非常缺乏。本研究回顾性分析2002年1月至2012年1月间合并有血流感染的肝移植受者的死亡危险因素。
方法：本回顾性研究期间,我院共实施135例肝移植,其中43例受者发生了77次血流感染。本研究使用单变量分析和多元逻辑回归以确定合并血流感染的肝移植的死亡危险因素。
结果：43例受者发生了血流感染(31-9%)。入选受者平均年龄45.1(45.1±14.1)岁。绝大多数为院内获得性感染(97.7%),超过半数的感染为复数菌感染(53.5%),24例发生死亡(55.8%)。单变量分析显示肝移植后血流感染相关死亡的危险因素为：腹腔内/胆道来源(P=0.011),复数菌感染(P=0.029),血小板计数<50,000/mm3(P=0.02),血肌酐值>1.5mg/dL (P=0.008),感染性休克(P<0.001)。多元逻辑回归分析显示血肌酐值>1.5mg/dL和感染性休克是肝移植后血流感染相关死亡的独立危险因素。
结论：与肝移植合并血流感染的死亡率显著相关的危险因素包括升高的血清肌酐值及感染性休克。因此有效预防肝移植受者血流感染的发生以及保护肾功能均十分重要。
第四章21例肝或肾移植术后血流感染病原菌分布及耐药性
目的：分析病原菌在肝或肾移植术后发生的血流感染中的分布情况及其耐药性特征,以期指导临床对抗生素进行合理使用。
方法：分析本院在2008年1月至2010年4月间的21例进行肝或肾移植术并术后发生血流感染的受者,21例血流感染的受者中共检出菌株24株,使用BD微生物鉴定系统进行药敏试验以了解病原菌分布及其耐药性。
结果：病原菌构成中包括占62.5%的G-杆菌及占37.5%的G+球菌。G-杆菌最敏感药物为喹诺酮(如环丙沙星)及碳青霉烯类(如美罗培南)抗生素。磺胺类及单环β内酰胺类(如氨曲南)抗生素耐药性最高,头孢类第一、二、三代抗生素(如头孢他啶)为其次；G+球菌最敏感药物的为糖肽类(如万古霉素)及恶唑烷酮类(如利奈唑胺)抗生素。
结论：本院2008年1月至2010年4月间肝或肾移植术后发生的血流感染中的病原菌以G-杆菌占优势,病原菌普遍对临床常用抗生素有较高的耐药性。
第二部分肾移植术后感染基因多态性研究
第一章IL-1家族基因多态性与肾移植后血流感染相关性
目的：血流感染在肾移植术后发病率及死亡率均高,目前暂无研究对IL-1家族基因多态性与肾移植术后血流感染发生敏感性的相关性进行调查。当前的研究因此对此进行调查以了解IL-1β(-511C/T)与IL-1受体拮抗剂(86bp可变数量串联重复)基因多态性与肾移植术后一年内发生的血流感染的相关性。
方法：选取21例术后一年内发生血流感染的肾移植受者作为调查对象及60例术后未发生感染的肾移植受者进行对照,自该81例肾移植受者的外周血白细胞以血液基因小量提取试剂盒提取全基因组DNA备用。包含AvaI酶切位点的区域通过PCR方法被扩增,该酶切位点位于IL-1β基因的-511位点处,扩增产物接着被限制性内切酶AvaⅠ消化。包含IL-1受体拮抗剂基因的86碱基对可变数量串联重复多态区域也通过PCR方法进行扩增。
结果：本研究发现单因素分析显示IL-1β-511CC基因型及IL-1β-511C等位基因在肾移植术后发生血流感染的受者中具有更高携带率(P值分别为0.023和0.015),未发现IL-1受体拮抗剂基因型和等位基因与肾移植术后血流感染的相关性(P值分别为0.508和0.507)；多因素分析表明,进行混杂因素调整后,IL-1β-511CC基因型(OR=4.400,95%CI=1.517-12.759, P=0.006)及IL-1β-511C等位基因(OR=2.444,95%CI：1.172-5.100,P=0.015)能够作为肾移植术后一年内发生血流感染的独立危险因素。
结论：本研究提供了肾移植受者IL-1β-511CC基因型及IL-1β-511C的等位基因与肾移植术后一年内发生血流感染具有相关性的证据,该研究结果提示基因型数据有助于提供更为精确预测血流感染发生的可能并有助于采取更好的保护血流感染易感者的策略。
第二章TNFβ、IL-10和IL-1家族基因多态性与肾移植后肺部感染相关性
目的：肾移植术后肺部感染发病率及死亡率均较高,本研究因此对于TNFβ、IL-10、IL-1β和IL-1受体拮抗剂基因多态性能否预测肾移植术后一年内发生肺部感染进行调查。
方法：受试者由33位肾移植术后发生肺部感染的受者及63位肾移植术后未发生感染的受者组成。96位受者的全基因组DNA自外周血白细胞中提取,包含NcoI、 RsaI和AvaI多态性位点的区域通过PCR的方法扩增,该三个位点分别位于TNFβ基因的+252位点、IL-10基因的-592位点以及IL-1β基因-511位点处,扩增产物分别被限制性内切酶NcoI、RsaI和AvaI消化,包含IL-1受体拮抗剂基因的86碱基对可变数量串联重复多态区域通过PCR方法扩增。
结果：单因素分析发现受体IL-10, IL-1β和IL-1受体拮抗剂基因多态性与肾移植术后发生肺部感染无关(P值分别为0.589,0.940和0.286)；然而与GG基因型相比较,受者TNFβ+252AA+AG基因型与肾移植术后肺部感染的发生显著相关(P=0.006)。进行多因素分析,经排除年龄因素影响,受者TNFβ+252AA+AG基因型能够成为独立预测肾移植术后一年内发生肺部感染的独立危险因素(OR=5.366,95%CI=1.470-19.589,P=0.011)。
结论：本研究提示受者TNFβ基因多态性可能成为肺部感染的独立危险因素,因此能够明确哪些受者能够从减少免疫抑制剂并加强预防感染的措施中受益。
第三章甘露糖结合凝集素-2基因多态性影响肾移植后血流感染发生
目的：甘露糖结合凝集素属于C型凝集素,主要依靠结合多种微生物表面的碳水化合物结构发挥作用。甘露糖结合凝集素-2基因在启动子区及外显子1区的基因多态性与甘露糖结合凝集素血清浓度降低有关,因之与移植术后的感染发生相关。本研究对甘露糖结合凝集素-2的基因型变异体与肾移植术后一年内发生的血流感染的相关性进行分析。
方法：前瞻性研究分析81例肾移植术后受者。对血流感染事件进行前瞻性收集。共对6个甘露糖结合凝集素-2基因的功能性单核苷酸变异点通过基因测序方法进行分析。
结果：多因素分析仅仅发现当与PP基因型进行比较时,受者甘露糖结合凝集素-2基因的5’非翻译区QQ+PQ基因型与血流感染的发生相关(OR=3.677,95%可信区间(CI)=1.127-11.998, P=0.031),没有发现甘露糖结合凝集素-2基因的其他5个单核苷酸变异与肾移植术后血流感染的发生相关。
结论：受者甘露糖结合凝集素-2基因的5’非翻译区QQ+PQ基因型与肾移植术后的血流感染的发生相关。
第四章纤维胶凝蛋白-2基因多态性预测肾移植后血流感染
目的：纤维胶凝蛋白-2的结构和功能与甘露糖结合凝集素相似,能与微生物表面的N-乙酰氨基葡糖相互作用,纤维胶凝蛋白-2启动子区及外显子8区基因多态性与血清中纤维胶凝蛋白-2浓度差异相关,并与移植术后感染相关。本研究结合其他影响因素评价纤维胶凝蛋白-2基因多态性与肾移植术后发生血流感染的相关性。
方法：前瞻性研究分析81例肾移植术后受者。共对5个纤维胶凝蛋白-2基因的功能性单核苷酸变异点通过PCR方法扩增后进行基因测序分析。血流感染事件进行前瞻性收集。对纤维胶凝蛋白-2的变异体与肾移植术后一年内发生的血流感染的相关性进行分析。
结果：单因素分析发现纤维胶凝蛋白-2基因的启动子区-986G/A位点变异体及外显子8区Thr236Met (+6359C>T)变异体与血流感染的发生率增高相关(P值均为0.016)。多因素分析仅发现外显子8区Thr236Met (+6359C>T)变异体与血流感染的高发生率相关(OR=4.917,95%可信区间(CI)=1.229-19.667, P=0.024)。未发现纤维胶凝蛋白-2基因的其他3个单核甘酸变异与发生血流感染相关。
结论：外显子8区Thr236Met(+6359C>T)变异体是肾移植术后发生血流感染的独立危险因素。
The present study includes part1Mortality and septic shock predictors of bloodstream infections in solid organ transplantation recipients, and part2Association between gene polymorphisms and infection after kidney transplantation. In part1, a retrospective study of133episodes of BSIs documented in98SOT patients was conducted to assess potential predictors of septic shock and mortality, and a retrospective study of77episodes of BSIs were observed following43of liver transplantation to assess risk factors for mortality. To determine the distribution of pathogens and their characteristics of drug susceptibility of bloodstream infections after renal or hepatic transplantation. The predictors significantly associated with increased mortality in SOT recipients with BSIs included decreased platelet count and septic shock. The risk factors for developing septic shock in SOT with bloodstream infections were early-onset (the2nd-8th week post transplant) and polymicrobial etiology. The risk factors significantly associated with increased mortality in liver transplant recipients with BSIs are higher serum creatinine levels and septic shock. Though gram positive coccus played an important role, most infections were caused by gram negative bacteria of bloodstream infections after renal or hepatic transplantation. The antibiotic resistant rate for gram negative bacteria was very high as well as gram positive coccus.
In part2, the study was conducted to determine the influence of the polymorphisms of interleukin-10(IL-113)(-511C/T)and IL-1receptor antagonist gene (IL-1RN)(86-bpVNTR) on the susceptibility to bloodstream infections within the first year after kidney transplantation, and investigate whether or not the polymorphisms of TNF β, IL-10, IL-1β and IL-1receptor antagonist (IL-lra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation. MBL2and FCN2genotypic variants were also analyzed for association with the incidence of bloodstream infections within the first year after kidney transplantation.
The present work provides evidence that recipient IL-1β-511CC genotype or IL-1β-511C allele is associated with the susceptibility to bloodstream infections within the first year after kidney transplantation and that recipient TNF β gene polymorphism may be useful in predicting pneumonia. Recipient QQ+PQ genotypes of MBL25'-UTR+4and recipient Thr236Met (+6359C>T) variant of exon8of FCN2have significant impact on the risk of developing bloodstream infections after kidney transplantation. There are17figures,18tables and135references.
Part1Mortality and septic shock predictors of bloodstream infections in solid organ transplantation recipients
Chapter I Mortality predictors of bloodstream infections in solid organ transplantation recipients
Objective:To assess the possible predictors influencing survival among solid organ transplantation(SOT) recipients with bloodstream infections(B SIs).
Methods:A retrospective study of133episodes of BSIs documented in98patients was conducted to assess potential predictors of mortality. The predictors were identified by univariate and multivariate logistic regression analyses.
Results:The mean age for the98enrolled patients was42.3years(42.3±12.8years). The majority of infections were nosocomial (79.6%), and the BSIs-related mortality rate was39.8%(39of98patients). The univariate analysis identified the following variables as predictors of BSIs-related mortality:intra-abdominal/biliary focus(P=0.011), polymicrobial infectionCP<0.001), liver transplant(P=0.002), platelet count<50,000/mm3(P<0.001), Lymphocyte count<300/mm3(P=0.027), and septic shock(P<0.001). The multivariate logistic regression analysis identified platelet count<50,000/mm3and septic shock as independent predictors of mortality.
Conclusion:The predictors significantly associated with increased mortality in SOT recipients with BSIs included decreased platelet count and septic shock. Although appropriate antimicrobial therapy, the BSIs-related mortality was very high. Special attention should be paid to schedule optimal strategies for BSIs control practices in a transplantation setting.
Chapter Ⅱ The risk factors for septic shock in solid organ transplantation recipients with bloodstream infections
Objective:To evaluate the risk factors for septic shock among solid organ transplant recipients with bloodstream infections.
Methods:A retrospective study consists of98subjects who underwent a kidney, heart transplant, simultaneous kidney-pancreas, liver-kidney, or orthotopic liver transplantation. All episodes of bloodstream infections significant according to the CDC criteria were analyzed.
Results:133episodes of bloodstream infections occurred in98patients, with39of them developing septic shock. Among39septic shock patients, bloodstream infections were due to polymicrobial in43.5%, gram-negative bloodstream infections in38.5%, gram-positive bloodstream infections in15.4%, and fungal in2.6%of patients. The lung was the most frequent source of bloodstream infections (41.8%), followed by intra-abdominal/biliary focus (24.5%). Empiric therapy was correct in72%of cases with shock. However,31(79%) patients died despite that20patients were adequate empiric antibiotic therapy. Risk factors for developing septic shock were the2nd to8th week post transplant (P=0.014), polymicrobial etiology (P=0.001), intra-abdominal/biliary focus (P=0.011), and liver transplant (P=0.002) Only the2nd to8th week post transplant and polymicrobial etiology were significant in multivariate analysis.
Conclusions:Our study revealed that risk factors for developing septic shock in SOT with bloodstream infections were early-onset (the2nd-8th week post transplant) and polymicrobial etiology.
Chapter III The Risk Factors for Mortality in Deceased Donor Liver Transplant Recipients with Bloodstream Infections
Objective:More data on the risk factors for mortality in liver transplant recipients with bloodstream infections (BSIs) are needed. From January2002to January2012, a retrospective analysis of BSIs in deceased donor liver transplant was reviewed.
Methods:During the retrospective study period,135deceased donor liver transplants were performed, and77episodes of BSIs were observed following43of them to assess risk factors for mortality. Risk factors were identified by univariate and multivariate logistic regression analysis.
Results:Forty-three of the recipients (31.9%) developed BSIs. The median age for these patients was45.1years(45.1±14.1years). The majority of infections were nosocomial (97.7%), and more than half were polymicrobial(53.5%). There were24deaths in these recipients (55.8%). The univariate analysis identified the following variables as the risk factors for BSIs-related mortality:Polymicrobial{P=0.029), platelet count<50,000/mm3(P=0.02), creatinine>1.5mg/dL (P=0.008), and septic shock(P<0.001). Multivariate logistic regression showed that the independent risk factors for mortality are creatinine>1.5mg/dL and septic shock.
Conclusion:The risk factors significantly associated with increased mortality in deceased donor liver transplant recipients with BSIs are higher serum creatinine levels and septic shock. Although appropriate antimicrobial treatment, BSIs accompanied by septic shock or higher serum creatinine levels are associated with high mortality rates. It is therefore essential to pay special attention to protection of renal function and effective control measures to reduce the incidence of BSIs.
Chapter IV Distribution of pathogen and resistance of BSIs after renal or hepatic transplantation:A clinical anylasis of21
Objective:To determine the distribution of pathogens and their characteristics of drug susceptibility of bloodstream infections after renal or hepatic transplantation, and to provide evidence for clinical anti-infection treatments.
Methods:Retrospective analysis to the pathogens and their drug susceptibility characteristics was carried out. These pathogens were isolated from the samples that came from patients with bloodstream infections after renal or hepatic transplantation from2008to2010.
Results:The main pathogens were gram negative bacteria (62.5%), and the next ones were gram positive bacteria (37.5%). The most common gram negative bacilli were Escherichia coli. While for gram positive bacteria, the main bacilli were Staphylococcus aureus. The gram negative bacteria were relatively sensitive to carbapenem and quinolone. The gram positive bacteria were sensitive to glycopeptides and oxazolidone.
Conclusions:Though gram positive coccus played an important role, most infections were caused by gram negative bacteria of bloodstream infections after renal or hepatic transplantation. The antibiotic resistant rate for gram negative bacteria was very high as well as gram positive coccus.
Part2Association between gene polymorphisms and infection after kidney transplantation
Chapter I Genetic association of interleukin-1βand its receptor antagonist gene polymorphisms with susceptibility to bloodstream infections in kidney transplant recipients
Objective:Bloodstream infections remain significant causes of morbidity and mortality after kidney transplantation. No study has investigated the association of IL-1cluster gene polymorphism with susceptibility to bloodstream infections in kidney transplant recipients so far. The present study was therefore, conducted to determine the influence of the polymorphisms of interleukin-1β (IL-1β)(-511C/T)and IL-1receptor antagonist gene (IL-1RN)(86-bpVNTR) on the susceptibility to bloodstream infections within the first year after kidney transplantation.
Methods:Subjects comprised21kidney transplant recipients with bloodstream infections and60noninfected kidney transplant recipients. Genomic DNA from these81kidney transplant recipients was extracted routinely from peripheral blood leukocytes. The region containing the Aval polymorphic site at position-511of IL-1β gene was amplified by polymerase chain reaction(PCR) and subsequently digested with AvaI restriction enzyme. The polymorphic regions within intron2of IL-1RN containing variable numbers of a tandem repeat (VNTR) of86base pairs were amplified by means of PCR.
Results:A higher presence of IL-1β-511CC genotype and IL-1β-511C allele in the recipients with bloodstream infections than in the noninfected recipients (P=0.023and P=0.015, respectively) was found. In contrast, the current study failed to show any significant difference, either in genotypic or allelic frequency for the IL-1RN polymorphism regarding the incidence of bloodstream infections (P=0.508and P=0.507, respectively). After adjusting, recipient IL-1β-511CC genotype (OR 4.400,95%CI=1.517-12.759, P=0.006) and recipient IL-1β-511C allele (OR=2.444,95%CI=1.172-5.100, P=0.015) predicted independently the risk for bloodstream infections within the first year after kidney transplantation.
Conclusion:The present work provides evidence that recipient IL-1β-511CC genotype or IL-1β-511C allele is associated with the susceptibility to bloodstream infections within the first year after kidney transplantation. These results suggest that genotyping data may allow more accurate prediction of bloodstream infections and the design of strategies to protect the most vulnerable patients.
Chapter Ⅱ Genetic association of tumor necrosis factor β, interleukin-10and interleukin-1gene cluster polymorphism with susceptibility to pneumonia in kidney transplant recipients
Objective:Pneumonia remains a significant cause of morbidity and mortality after kidney transplantation. The present study was therefore, conducted to investigate whether or not the polymorphisms of TNF β, IL-10, IL-1β and IL-1receptor antagonist (IL-lra) gene predicted the susceptibility to pneumonia within the first year after kidney transplantation.
Methods:Subjects comprised33kidney transplant recipients with pneumonia and63non-infected kidney transplant recipients. Genomic DNA from these96kidney transplant recipients was extracted from peripheral blood leukocytes. The regions containing the Ncol polymorphic site at position+252of TNF β gene, the RsaI polymorphic site at position-592of IL-10gene and the Aval polymorphic site at position-511of IL-1β gene were amplified by polymerase chain reaction(PCR) and subsequently digested with Ncol, RsaI and Aval restriction enzyme, respectively. The polymorphic regions within intron2of IL-lra gene (IL-1RN) containing variable numbers of a tandem repeat (VNTR) of86base pairs, were amplified by PCR.
Results:Individual locus analysis showed that recipient IL-10, IL-1β and IL-1RN polymorphisms were not associated with the presence of pneumonia (P=0.589,0.940and0.286, respectively). However, compared with GG genotype, recipient TNF β+252AA+AG genotype was significantly associated with susceptibility to pneumonia (P=0.006). After adjusting for age of45years or older, recipient TNF β+252AA+AG (OR=5.366,95%confidence intervals (CI)=1.470-19.589, P0.011) independently predicted the risk for pneumonia within the first year after kidney transplantation.
Conclusion:These results suggested that recipient TNF β gene polymorphism may be useful in predicting pneumonia hence identifying individuals that could benefit from preventive treatment and a less potent immunosuppression regimen.
Chapter III Mannose-binding lectin gene polymorphisms influence the susceptibility to bloodstream infections in kidney transplant recipients
Objective:Mannose-binding lectin (MBL) is a C-type lectin that interacts with carbohydrate structures on microbial surfaces. Polymorphisms at the promoter and exon1of the MBL2gene are responsible for low serum levels of MBL and have been shown to play an important role in an increased risk of post-transplant infections. MBL2genotypic variants were analyzed for association with the incidence of bloodstream infections within the first year after kidney transplantation.
Methods:We prospectively analyzed81kidney transplant recipients. A total of6well-known functional Single-nucleotide polymorphisms(SNPs) in the MBL2gene of the recipients were determined by gene sequencing. The events of bloodstream infections were collected prospectively.
Results:Multivariate analyses only found an association of recipient QQ+PQ genotypes of MBL25'-UTR+4with the incidence of bloodstream infections (OR=3.677,95%confidence intervals (CI)=1.127-11.998, P=0.031) as compared to PP genotypes of MBL25'-UTR+4. No differences were found according to other5polymorphisms in the MBL2gene.
Conclusion:Recipient QQ+PQ genotypes of MBL25'-UTR+4have significant impact on the risk of developing bloodstream infections after kidney transplantation.
Chapter IV Gene polymorphisms of ficolin-2predict bloodstream infections risk after kidney transplantation
Objective:Ficolin-2interacts with N-acetylglucosamine on microbial surfaces and has similarities in structure and function to Mannose-binding lectin (MBL). Polymorphisms in the promoter region and exon8of the ficolin-2(FCN2) gene are responsible for differences in ficolin-2serum levels and have been shown to play an important role in an increased risk of post-transplant infections. We assessed the relationship between these polymorphic genes and bloodstream infections within the first year after kidney transplantation, in relation to major risk factors.
Methods:We prospectively analyzed81kidney transplant recipients. A total of5well-known functional Single-nucleotide polymorphisms(SNPs) in the FCN2gene of the recipients were determined by gene sequencing. Bloodstream infections events were collected prospectively. FCN2genotypic variants were analyzed for association with the incidence of bloodstream infections within the first year after kidney transplantation.
Results:Univariate analysis found-986G/A variant of promoter region(P=0.016) and Thr236Met (+6359OT) variant of exon8(P=0.016) are associated with the incidence of bloodstream infections. Multivariate analysis only found an association of recipient Thr236Met (+6359C>T) variant of exon8with the incidence of bloodstream infections (OR=4.917,95%confidence intervals (CI)=1.229-19.667, P=0.024). No differences were found according to other3polymorphisms in the FCN2gene.
Conclusion:Recipient Thr236Met (+6359C>T) variant of exon8are major determinants of the risk of developing bloodstream infections after kidney transplantation.
引文
[1]Kim S, Kim Y, Jun Y, et al. Epidemiology and risk factors for bacteremia in 144 consecutive living-donor liver transplant recipients[J]. Yonsei Med J 2009,50(1): 112-121.
[2]Wagener MM, Yu VL. Bacteremia in transplant recipients:a prospective study of demographics, etiologic agents, risk factors and outcomes[J]. Am J Infect Control 1992,20:239-247.
[3]A. Morenoa, C. Cerveraa, J. Gavald, et al. Bloodstream infections among transplant recipients:results of a nationwide surveillance in Spain[J]. Am J Transplant 2007,7:2579-2586.
[4]Wade JJ, Rolando N, Hayllar K, et al. Bacterial and fungal infections after liver transplantation:an analysis of 284 patients[J]. Hepatology 1995,21:1328-1336.
[5]Singh N, Gayowski T, Wagener MM, et al. Predictors and outcome of early-versus late-onset major bacterial infections in liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression[J]. Eur J Clin Microbiol Infect Dis 1997,16:821-826.
[6]Singh N, Wagener MM, Obman A, et al. Bacteremias in liver transplant recipients:shift toward gram-negative bacteria as predominant pathogens[J]. Liver Transpl 2004,10:844-849.
[7]Taku Iida, Toshimi Kaido, Shintaro Yagi, et al. Posttransplant bacteremia in adult living donor liver transplant recipients [J]. Liver Transpl 2010,16:1379-1385.
[8]Rabkin DG, Stifelman MD, Birkhoff J, et al. Early catheter removal decreases incidence of urinary tract infections in renal transplant recipients[J]. Transplant Proc 1998,30:4314-4316.
[9]Osman Y, Ali-El-Dein B, Shokeir AA, et al. Routine insertion of ureteral stent in live-donor renal transplantation:Is it worthwhile[J]. Urol 2005,65:867-871.
[10]Candel FJ, Grima E, Matesanz M, et al. Bacteremia and septic shock after solid-organ transplantation[J]. Transplant Proc 2005,37:4097-4099.
[11]J. Hsu, D. R. Andes, V. Knasinski, et al. Statins are associated with improved outcomes of bloodstream infection in solid-organ transplant recipients[J]. Eur J Clin Microbiol Infect Dis 2009,28:1343-1351.
[12]Maricar F. Malinis, Steven D. Mawhorter, Anil Jain, et al. Staphylococcus aureus bacteremia in solid organ transplant recipients:Evidence for improved survival when compared with nontransplant patients[J]. Transplantation 2012,93:1045-1050.
[13]Weinstein MP, Towns ML, Quartey SM, et al. The clinical of positive blood cultures in the 1990s:A prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults[J]. Clin Infect Dis 1997,24(4):584-602.
[14]Singh N, Paterson DL, Gayowski T, et al. Predicting bacteremia and bacteremic mortality in liver transplant recipients[J]. Liver Transpl 2000,6:54-61.
[15]Frederic Bert, Beatrice Larroque, Catherine Paugam-Burtz, et al:Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients:An analysis of 259 episodes[J]. Liver Transpl 2010,16:393-401.
[16]Palmer SM, Alexander BD, Sanders LL, et al. Significance of blood stream infection after lung transplantation:Analysis in 176 consecutive patients[J]. Transplant 2000,69:2360-2366.
[17]Silveira FP, Marcos A, Kwak EJ, et al. Bloodstream infections in organ transplant recipients receiving alemtuzumab:No evidence of occurrence of organisms typically associated with profound T cell depletion[J]. J Infect 2006,53:241-247.
[18]Plevak DJ, Southorn PA, Narr BJ. Intensive care unit experience in the Mayo liver transplant program:the first 100 cases[J]. Mayo Clin Proc 1989,64: 433-445.
[19]Shieh RM, Chen CL, Wang KL. Respiratory changes and pulmonary complications following orthotopic liver transplantation[J].Transplant Proc 1992,24: 1486-1488.
[20]J. Torre-Cisneros, C. Herrero, E. Canas, et al:High mortality related with staphylococcus aureus bacteremia after liver transplantation[J]. Eur J Clin Microbiol Infect Dis 2002,21:385-388.
[21]Patterson DL, Singh N, Gayowski T, et al. Rapidly fatal bacteremia due to Staphylococcus aureus producing both enterotoxins A and B in a liver transplant recipient[J]. Clinical Infectious Diseases 1997,25:1481-1482.
[22]Husain S, Tollemar J, Dominguez EA, et al. Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients:Prospective, multicenter, case-controlled study[J]. Transplantation 2003,75:2023-2029.
[23]Shi SH, Kong HS, Xu J, et al. Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients[J]. Transplant Infect Dis 2009,11:405-412.
[24]Moacyr Silva, Jr, Alexandre R. Marra, Carlos A. P. Pereira, et al. Bloodstream infection after kidney transplantation:Epidemiology, microbiology, associated risk factors, and outcome[J]. Transplantation 2010,90:581-587.
[25]Majdi N. Al-Hasan, Raymund R. Razonable, Walter K. Kremers, et al. Impact of gram-negative bloodstream infection on long-term allograft survival after kidney transplantation[J].Transplantation 2011,91:1206-1210.
[26]Danziger-Isakov LA, Sweet S, Delamorena M, et al. Epidemiology of bloodstream infections in the first year after pediatric lung transplantation[J]. Pediatric Infect Dis J 2005,24:324-330.
[27]Rodriguez C, Munoz P, Rodriguez-Creixems M, et al. Bloodstream infections among heart transplant recipients[J]. Transplantation 2006,81:384-391.
[28]Akhter K, Timpone J, Matsumoto C, et al. Six-month incidence of bloodstream infections in intestinal transplant patients[J]. Transpl Infect Dis 2012, 14(3):242-247.
[29]McClean K, Kneteman N, Taylor G. Comparative risk of bloodstream infection in organ transplant recipients[J]. Infect Control Hosp Epidemiol 1994,15(9): 582-584.
[30]Moreno A, Mensa J, Almela M, et al.138 Episodes of bacteremia or fungemia in patients with solid organ (renal or hepatic) transplantation[J]. Med Clin (Bare) 1994,103(5):161-164.
[31]Sang-Oh Lee, Seung H. Kang, Rima C. Abdel-Massih, et al. Spectrum of early-onset and late-onset bacteremias after liver transplantation:Implications for management[J]. Liver Transpl 2011,17(6):733-741.
[32]Linares, J.F. Garcla-Goez, C. Cervera, et al. Early bacteremia after solid organ transplantation[J]. Transplantation Proc 2009,41(6):2262-2264.
[33]Hashimoto M, Sugawara Y, Tamura S, et al. Bloodstream infection after living donor liver transplantation[J]. Scand J Infect Dis 2008,40:509-516.
[34]Ron-Bin Hsu, Chung-I Chang, Chi-Tai Fang, et al. Bloodstream infection in heart transplant recipients:12-year experience at a university hospital in Taiwan[J]. EUR J CARDIO-THORAC 2011,40:1362-1367.
[35]Diana F. Florescu, Fang Qiu, Alan N. Langnas, et al. Bloodstream infections during the first year after pediatric small bowel transplantation[J]. Pediatr Infect Dis J 2012,31:700-704.
[36]Sigurdsson L, Reyes J, Kocoshis SA, et al. Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease[J]. Transplantation 2000,70:302-305.
[37]Garner JS, Jarvis WR, Emori TG, et al. CDC definitions of nosocomial infections[J]. Am J Infect Control 1988,16:128-140.
[38]Levry MM, Fink MP, Marshall JC, et al, for the international sepsis definitions conference.2001 SCCM/ESICM/ACCP/ATS/SIS International sepsis definition conference[J]. Intensive Care Med 2003,29:530-538.
[39]秦文,张剑,李茜,等.ICU获得性血流感染致病菌的临床分析[J].山东大学学报(医学版),2007,45(3)：265-268.
[40]Karunakaran R, Raja NS, Quek KF, et al.Evaluation of the routine use of the anaerobic bottle when using the BACTEC blood culture system[J]. J Microbiol Immunol Infect 2007,40(5):445-449.
[41]Leigh DA. Bacteraemia in patients receiving human cadaveric renal transplants[J]. J Clin Pathol 1971,24:295-299.
[42]Nielsen HE, Korsager B. Bacteremia after renal transplantation[J]. Scand J Infect Dis 1977,9:111-117.
[43]Morduchowicz G, Pitlik SD, Shapira Z, et al. Infections in renal transplant recipients in Israel[J]. Isr J Med Sci 1985,21:791-797.
[44]Lin MF, Lau YJ, Hu BS, et al. Bacteremia in renal transplant recipients: Retrospective analysis of 60 episodes in a teaching hospital[J]. Zhonghua Yi Xue Za Zhi (Taipei) 2001,64:108-114.
[45]Kusne S, Dummer JS, Singh N, et al. Infections after liver transplantation, an analysis of 101 consecutive cases[J]. Medicine 1988,67:132-143.
[46]George DL, Arnow PM, Fox AS, et al. Bacterial infection as a complication of liver transplantation:Epidemiology and risk factors[J]. Review of Infectious Disease 1991,13:387-396.
[47]张卓然,倪语星.临床微生物学和微生物检验[M].北京：人民卫生出版社,2003,3：503-505.
[48]刘剑荣,张勇,陈玲,等.280例血培养阳性标本细菌分布及耐药性分析[J].检验医学与临床,2009,6(4)：279-280.
[49]Leite JL, Manfrinatto JA, Mazzali M, et al. Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients[J]. Transplant Int 2006,19:732-737.
[50]Ducloux D, Deschamps M, Yannaraki M, et al. Relevance of Toll-like receptor-4 polymorphisms in renal transplantation[J]. Kidney Int 2005,67: 2454-2461.
[51]Kimball P, Reid F. Tumor necrosis factor gene polymorphisms associated with urinary tract infections after renal transplantation[J]. Transplantation 2002,73: 1110-1112.
[52]Sahoo S, Kang S, Supran S, et al. Tumor necrosis factor genetic polymorphisms correlate with infections after renal transplantation[J]. Transplantation 2000,69:880-884.
[53]E. Rodrigo, P. Sanchez-Velasco, J.C. Ruiz, et al. Cytokine polymorphisms and risk of infection after kidney transplantation[J]. Transplantation Proc 2007,39: 2219-2221.
[54]郭义峰,谭建明,李荣宇,等.肾移植受者的细胞因子及其受体单核苷酸多态性与术后感染的相关性[J].中华器官移植杂志,2005,26(9)：531-535.
[55]顾新伟,赵明,范礼佩,等.TNFa基因多态性在老年人肾移植受者感染中的作用[J].中国医师杂志,2004,6(3)：322-323.
[56]羊继平,齐隽,闵志廉,等.肾移植受者细胞因子基因多态性与术后发生感染的关系[J].中华器官移植杂志,2005,26(2)：97-99.
[57]Alakulppi NS, Kyllonen LE, Salo HME, et al. The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation[J]. Transpl Immunol 2006,16:258-262.
[58]McClean K, Kneteman N, Taylor G. Comparative risk of bloodstream infection in organ transplant recipients[J]. Infect Control Hosp Epidemiol 1994,15: 582-584.
[59]Moreno A, Mensa J, Almela M, et al.138 Episodes of bacteremia or fungemia in patients with solid organ (renal or hepatic) transplantation[J]. Med Clin (Bare) 1994,103:161-164.
[60]Wagener MM, Yu VL. Bacteremia in transplant recipients:a prospective study of demographics, etiologic agents, risk factors and outcomes[J]. Am J Infect Control 1992,20:239-247.
[61]Jason W. Chi en, Michael J. Boeckh, John A. Hansen, et al. Lipopolysaccharide binding protein promoter variants influence the risk for gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation[J]. Blood 2008,111:2462-2469.
[62]Mensah Nana Yaa, Peterlongo Paolo, Steinherz Peter, et al. Toll-Like receptor 4 polymorphisms and risk of gram-negative bacteremia after allogeneic stem cell transplantation. A prospective pilot study[J], Biol Blood Marrow Transplant 2009, 15:1130-1133.
[63]Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases[J]. Clin Infect Dis 2003,37:1496-1505.
[64]Medzhitov R, Janeway C Jr. Innate immunity[J]. N Engl J Med 2000,343: 338-344.
[65]Minchinton RM, Dean MM, Clark TR, et al. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an ustralian blood donor population[J]. Scand J Immunol 2002,56:630-641.
[66]Crosdale DJ, Ollier WE, Thomson W, et al. Mannose-binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids[J]. Eur J Immunogenet 2000,27:111-117.
[67]Turner MW, Hamvas RM. Mannose-binding lectin:structure, function, genetics and disease associations[J]. Rev Immunogenet 2000,2:305-322.
[68]Madsen HO, Garred P, Thiel S, et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein[J]. J Immunol 1995,155:3013-3020.
[69]Garred P, Madsen HO, Svejgaard A, et al. Mannose-binding lectin and meningococcal disease[J]. Lancet 1999,354:336, author reply 337.
[70]Worthley DL, Johnson DF, Eisen DP, et al. Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation[J]. Clin Infect Dis 2009,48:410-417.
[71]de Rooij BJ, van Hoek B, Ten Hove WR, et al. Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation[J]. HEPATOLOGY 2010,52:1100-1110.
[72]Bouwman LH, Roos A, Terpstra OT, et al. Mannose-binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation[J]. Gastroenterology 2005,129:408-414.
[73]de Rooij BJ, van der Beek MT, van Hoek B, et al. Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation[J]. J Hepatol 2011,55(4):800-807.
[74]Cervera C, Lozano F, Linares L, et al. Influence of mannose-binding lectin gene polymorphisms on the invasiveness of cytomegalovirus disease after solid organ transplantation[J]. Transplant Proc 2009,41(6):2259-2261.
[75]Verschuren JJ, Roos A, Schaapherder AF, et al. Infectious complications after simultaneous pancreas-kidney transplantation:A role for the lectin pathway of complement activation[J]. Transplantation 2008,85(1):75-80.
[76]Cervera C, Lozano F, Saval N, et al. The influence of innate immunity gene receptors polymorphisms in renal transplant infections[J]. Transplantation 2007, 83(11):1493-1500.
[77]Matsushita M, Endo Y, Taira S, et al. A novel human serum lectin with collagen-and fibrinogen-like domains that functions as an opsonin[J]. J Biol Chem 1996,271:2448-2454.
[78]Ma YG, Cho MY, Zhao M, et al. Human mannose-binding lectin and 1-ficolin functions specific pattern recognition proteins in the lectin activation pathway of complement[J]. J Biol Chem 2004,279:23307-23312.
[79]Matsushita M, Fujita T. Ficolins and the lectin complement pathway[J]. Immunol Rev 2001,180:78-85.
[80]Thiel S. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins[J]. Mol Immunol 2007,44(16):3875-3888.
[81]Runza VL, Schwaebleb W, Mannel DN. Ficolins:Novel pattern recognition molecules of the innate immune response[J].1 mmuuobiology 2008,213(3-4): 297-306.
[82]Kilpatrick D.C., Fujita T. and Matsushita M. P35, an opsonic lectin of the ficolin family, in human blood from neonates, normal adults, and recurrent miscarriage patients[J]. Immunol Lett 1999,67:109-112.
[83]Taira S., Kodama N., Matsushita M., et al. Opsonic function and concentration of human serum ficolin/P35[J]. Fukushima J Med Sci 2000,46:13-23.
[84]Endo Y, Sato Y, Matsushita M, et al. Cloning and characterization of the human lectin P35 gene and its related gene[J]. Genomics 1996,36:515-521.
[85]Sugimoto R, Yae Y, Akaiwa M, et al.Cloning and characterization of the Hakata antigen, a member of the Ficolin/opsonin p35 lectin family[J]. J Biol Chem 1998,273:20721-20727.
[86]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2[J]. Hum Mol Genet 2005,14:1651-1658.
[87]Haerynck F, Van Steen K, Cattaert T, et al. Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients[J]. Hum Immunol 2012,73(11):1175-1183.
[88]Cedzynski M, Nuytinck L, Atkinson AP, et al. Extremes of L-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene[J]. Clin Exp Immunol.2007,150(1): 99-104.
[89]Ouf EA, Ojurongbe O, Akindele AA, et al. Ficolin-2 levels and FCN2 genetic polymorphisms as a susceptibility factor in schistosomiasis[J]. J Infect Dis 2012,206(4):562-570.
[90]Meijvis SC, Herpers BL, Endeman H, et al. Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on peritoneal dialysis with staphylococcal peritonitis[J]. Nephrol Dial Transplant 2011,26(3):1042-1045.
[91]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns[J]. Mol Immunol 2008,45:2508-2520.
[92]Munthe-Fog L, Hummelshoj T, Hansen BE, Koch C, et al. The impact of FCN2 polymorphisms and haplotypes on the Ficolin-2 serum levels[J]. Scand J Immunol 2007,65:383-392.
[93]Atkinson AP, Cedzynski M, Szemraj J, et al. L-ficolin in children with recurrent respiratory infections[J]. Clin Exp Immunol 2004,138:517-520.
[94]Chapman SJ, Vannberg FO, Khor CC, et al. Functional polymorphisms in the FCN2 gene are not associated with invasive pneumococcal disease[J]. Mol Immunol 2007,44:3267-3270.
[95]Ruskamp JM, Hoekstra MO, Postma DS, et al. Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children[J]. Clin Exp Immunol 2009,155:433-440.
[96]Faik I, Oyedeji SI, Idris Z, et al. Ficolin-2 levels and genetic polymorphisms of FCN2 in malaria[J]. Hum Immunol 2011,72:74-79.
[97]Messias-Reason I, Kremsner PG, Kun JF. Functional haplotypes that produce normal ficolin-2 levels protect against clinical leprosy[J]. J Infect Dis 2009, 199:801-804.
[98]Messias-Reason IJ, Schafranski MD, Kremsner PG, et al. Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease[J]. Clin Exp Immunol 2009,157:395-399.
[99]Hoang TV, Toan NL, Song le H, et al. Ficolin-2 Levels and FCN2 Haplotypes Influence Hepatitis B Infection Outcome in Vietnamese Patients[J]. PLoS One.2011,6(11):e28113.
[100]Liu J, Ali MA, Shi Y, et al. Specifically binding of L-ficolin to N-glycans of HCV envelope glycoproteins E1 and E2 leads to complement activation[J]. Cell Mol Immunol 2009,6:235-244.
[101]Amal Assaf, Tong Van Hoang, Imad Faik, et al. Genetic evidence of functional ficolin-2 haplotype as susceptibility factor in cutaneous leishmaniasis[J]. PLoS One.2012,7(3):e34113.
[102]Roos A, Rastaldi MP, Calvaresi N, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease[J]. Journal of the American Society of Nephrology 2006,17:1724-1734.
[103]Damman J, Kok JL, Snieder H, et al. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation [J]. Mol Immunol.2012,50(1-2):1-8.
[104]Cseh S, Vera L, Matsushita M, et al. Characterization of the interaction between L-ficolin/p35 and mannan-binding lectin-associated serine proteases-1 and-2[J]. J Im muno 2002,169:5735-5743.
[105]Babel N, Cherepnev G, Kowalenko A, et al. Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants[J]. Kidney Int 2004,66:428-432.
[106]Sainz J, Perez E, Gomez-Lopera S, et al. IL-1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate c-reactive protein level[J]. J Clin Immunol 2008,28(5):473-485.
[107]ZHANG Jian, LI Wei-ning, LIN Hua, et al. Genetic polymorphisms of interleukin-10 gene promoter-592 A/C site with hepatitis B virus infection[J]. J Mod Lab Med 2007,22(3):81-84.
[108]Arend WP, Malyak M, Guthridge CJ, et al. Interleukin-1 receptor antagonist:Role in biology[J]. Annu Rev Immunol 1998,16:27-55.
[109]Surbatovic M, Grujic K, Cikota B, et al. Polymorphisms of genes encoding tumor necrosis factor-alpha, interleukin-10, cluster of differentiation-14 and interleukin-lra in critically ill patients[J]. J Crit Care 2010,25(3):542. el-8.63.
[110]Jacob CO, Fronek Z, Lewis GD, et al. Heritable major histocompatibility complex class Ⅱ-associated production of tumor necrosis factor [alpha]:relevance to genetic predisposition to systemic lupus erythematous[J]. Proc Natl Acad Sci USA 1990,87(3):1233-1237.
[111]Jacob CO. Genetic variability in tumor necrosis factor production: relevance to predisposition to autoimmune diseases[J]. Reg Immunol 1992,4(5): 298-304.
[112]Bernal W, Donaldson P, Wendon J. Proinflammatory cytokine genomic polymorphism and critical illness[M]. In:Yearbook of Intensive Care Medicine. Vincent JL (Ed). Berlin, Springer 1999, pp 10-18.
[113]Watanabe E, Hirasawa H, Oda S, et al. Extremely high interleukin-6 blood levels and outcome in the critically ill are associated with tumor necrosis factor- and interleukin-1-related gene polymorphisms[J]. Crit Care Med 2005,33:89-97.
[114]Shu Q, Fang X, Chen Q, et al. IL-10 polymorphism is associated with increased incidence of severe sepsis[J]. Chin Med J 2003,116:1756-1759.
[115]Gong MN, Thompson BT, Williams PL, et al. Interleukin-10 polymorphism in position-1082 and acute respiratory distress syndrome[J]. Eur Respir J 2006,27:674-681.
[116]Messer G, Spengler U, Jung MC, et al. Polymorphic structure of tumor necrosis factor (TNF) locus:an Ncol polymorphism in the first intron of the TNF-beta gene correlates with a variant amino acid in position 26 and reduced level of TNF-beta production[J]. J Exp Med 1991,173(1):209-219.
[117]Piciot F, Molvig J, Wogensen L, et al. A tumor necrosis factor beta polymorphism in relation to monokine secretion and insulin-dependent diabetes mellitus[J]. Scand J Immunol 1991,33 (1):37-49.
[118]Pociot F, Briant L, Jongeneel CV, et al. Association of tumor necrosis factor (TNF) and class Ⅱ major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells:a possible link to insulin-dependent diabetes mellitus[J]. Eur J Immunol 1993,23:224-231.
[119]Riese J, Woerner K, Zimmermann P, et al. Association of a TNFb gene polymorphism with complications after major abdominal operations[J]. Shock 2003, 19:1-4.
[120]Watanabe E, Buchman H, Hirasawa H, et al. Association between lymphotoxin-[alpha] (tumor necrosis factor-[beta]) intron polymorphism and predisposition to severe sepsis is modified by gender and age[J]. Crit Care Med 2010, 38(1):181-193.
[121]Cervera C, Balderramo D, Suarez B, et al. Donor mannose-binding lectin gene polymorphisms influence the outcome of liver transplantation[J]. Liver Transpl 2009,15 (10):1217-1224.
[122]Rantala A, Lajunen T, Juvonen R, et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men[J]. J Infect Dis 2008,198:1247-1253.
[123]Steffensen R, Thiel S, Varming K, et al. Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers[J]. J Immunol Methods 2000,241:33-42.
[124]Neth O, Jack DL, Dodds AW, et al. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition[J]. Infect Immun 2000,68:688-693.
[125]Petersen KA, Matthiesen F, Agger T, et al. Phase I safety, tolerability, and pharmacokinetic study of recoMBLnant human mannanbinding lectin[J]. J Clin Immunol 2006,26:465-475.
[126]Summerfield JA. Clinical potential of mannose-binding lectin-replacement therapy[J]. Biochem Soc Trans 2003,31:770-773.
[127]Valdimarsson H. Infusion of plasma-derived mannan-binding lectin (MBL) into MBL-deficient humans[J]. Biochem Soc Trans 2003,31:768-769.
[128]Valdimarsson H, Vikingsdottir T, Bang P, et al. Human plasma-derived mannose-binding lectin:a phase I safety and pharmacokinetic study[J]. Scand J Immunol 2004,59:97-102.
[129]Matsushita M, Fujita T. Activation of the classical complement pathway by mannose-binding protein in association with a novel Cls-like serine protease[J]. J Exp Med 1992,176:1497-1502.
[130]Matsushita M, Endo Y, Fujita T. Cutting edge:complement-activating complex of ficolin and mannose-binding lectin-associated serine protease[J]. J Immunol 2000,164:2281-2284.
[131]Petersen, S.V., Thiel, S., Jensenius, J.C. The mannan-binding lectin pathway of complement activation:biology and disease association[J]. Mol Immunol 2001,38:133-149.
[132]Damman J, Kok JL, Snieder H, et al. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation[J]. Mol Immunol.2012,50(1-2):1-8.
[133]Kilpatrick DC, McLintock LA, Allan EK, Copland M, Fujita T, Jordanides NE, et al. No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections[J]. Clin Exp Immunol 2003,134:279-284.
[134]Schlapbach LJ, Mattmann M, Thiel S, Boillat C, Otth M, Nelle M, et al. Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis[J]. Clin Infect Dis 2010,51:153-162.
[135]Atkinson AP, Cedzynski M, Szemraj J, St Swierzko A, Bak-Romaniszyn L, et al. L-ficolin in children with recurrent respiratory infections[J]. Clin Exp Immunol 2004,138:517-520.
[1]Wagener MM, Yu VL. Bacteremia in transplant recipients:A prospective study of demographics, etiologic agents, risk factors and outcomes[J]. Am J Infect Control 1992,20:239-247.
[2]McClean K, Kneteman N, Taylor G. Comparative risk of bloodstream infection in organ transplant recipients[J]. Infect Control Hosp Epidemiol 1994,15: 582-584.
[3]Moreno A, Mensa J, Almela M, et al.138 Episodes of bacteremia or fungemia in patients with solid organ (renal or hepatic) transplantation[J]. Med Clin (Barc) 1994,103:161-164.
[4]Sang-Oh Lee, Seung H. Kang, Rima C. Abdel-Massih, et al. Spectrum of early-onset and late-onset bacteremias after liver transplantation:Implications for management J]. Liver Transpl 2011,17(6):733-741.
[5]L. Linares, J.F. Garcla-Goez, C. Cervera, et al. Early bacteremia after solid organ transplantation[J]. Transplantation Proc 2009,41(6):2262-2264.
[6]Palmer SM, Alexander BD, Sanders LL, et al. Significance of blood stream infection after lung transplantation:Analysis in 176 consecutive patients[J]. Transplant 2000,69:2360-2366.
[7]A. Morenoa, C. Cerveraa, J. Gavald, et al. Bloodstream infections among transplant recipients:results of a nationwide surveillance in Spain[J]. Am J Transplant 2007,7(11):2579-2586.
[8]Kim S, Kim Y, Jun Y, et al. Epidemiology and risk factors for bacteremia in 144 consecutive living-donor liver transplant recipients[J]. Yonsei Med J 2009,50(1): 112-121.
[9]Taku Iida, Toshimi Kaido, Shintaro Yagi, et al. Posttransplant bacteremia in adult living donor liver transplant recipients[J]. Liver Transpl 2010,16:1379-1385.
[10]Hashimoto M, Sugawara Y, Tamura S, et al. Bloodstream infection after living donor liver transplantation[J]. Scand J Infect Dis 2008,40:509-516.
[11]Ron-Bin Hsu, Chung-I Chang, Chi-Tai Fang, et al. Bloodstream infection in heart transplant recipients:12-year experience at a university hospital in Taiwan[J]. EUR J CARDIO-THORAC 2011,40:1362-1367.
[12]Diana F. Florescu, Fang Qiu, Alan N. Langnas, et al. Bloodstream infections during the first year after pediatric small bowel transplantationfJ]. Pediatr Infect Dis J 2012,31:700-704.
[13]Sigurdsson L, Reyes J, Kocoshis SA, et al. Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease[J]. Transplantation 2000,70:302-305.
[14]Akhter K, Timpone J, Matsumoto C, et al. Six-month incidence of bloodstream infections in intestinal transplant patients[J]. Transpl Infect Dis 2012, 14(3):242-247.
[15]Singh N, Paterson DL, Gayowski T, et al. Predicting bacteremia and bacteremic mortality in liver transplant recipients[J]. Liver Transpl 2000,6(1):54-61.
[16]Singh N, Paterson DL, Chang FY, et al. Methicillin-resistant Staphlococcus aureus:The other emerging resistant Gram-positive coccus among liver transplant recipients[J]. Clin Infect Dis 2000,30:332-327.
[17]Bert F, Galdbart J-O, Zarrouk V, et al. Association between Staphylococcus aureus nasal carriage and infection in liver transplant recipients[J]. Clin Infect Dis 2000,31:1295-1299.
[18]Bert F, Bellier C, Lassel L, et al. Risk factors for Staphylococcus aureus infection for liver transplant recipients[J]. Liver Transpl 2005,11:1093-1099.
[19]Frederic Bert, Beatrice Larroque, Catherine Paugam-Burtz, et al. Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients:An analysis of 259 episodes[J]. Liver Transpl 2010,16:393-401.
[20]Bedini A, Codeluppi M, Cocchi S, et al. Gram-positive bloodstream infections in liver transplant recipients:Incidence, risk factors, andimpact on survival[J]. Transplant Proc 2007,39:1947-1949.
[21]Husain S, Tollemar J, Dominguez EA, et al. Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients:Prospective, multicenter, case-controlled study[J]. Transplantation 2003,75:2023-2029.
[22]Bellier C, Bert F, Durand F, et al. Risk factors for Enterobacteriaceae bacteremia after liver transplantation[J]. Transpl Int 2008,21:755-763.
[23]Falagas ME, Snydman DR, Griffith J, Werner BG, the Boston Center for Liver Transplantation CMVIG Study Group. Exposure to cytomegalovirus from the donated organ is a risk factor for bacteremia in orthotopic liver transplant recipients[J]. Clin Infect Dis 1996,23:468-474.
[24]Toshimi Kaido, Akira Mori, Yasuhiro Ogura, et al. Pre-and perioperative factors affecting infection after living donor liver Transplantation[J]. Nutrition 2012, 28:1104-1108.
[25]Shi SH, Kong HS, Xu J, et al. Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients[J]. Transplant Infect Dis 2009,11:405-412.
[26]SHI Shao-hua, KONG Hai-shen, JIA Chang-ku, et al. Coagulase-negative staphylococcus and enterococcus aspredominant pathogens in liver transplant recipients with gram-positive coccal bacteremia[J]. Chinese Medical Journal 2010, 123(15):1983-1988.
[27]Saner FH, Olde Damink SWM, Pavlakovic G, et al. Pulmonary and bloodstream infections in adult living donor and cadaveric liver transplant patientsfJ]. Transplantation 2008,85:1564-1568.
[28]K.W. Rhee, S.H. Oh, K.M. Kim, et al. Early bloodstream infection after pediatric living donor living transplantation[J]. Transplant Proc 2012,44:794-796.
[29]Weinstein MP, Towns ML, Quartey SM, et al. The clinical of positive blood cultures in the 1990s:A prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults[J]. Clin Infect Dis 1997,24(4):584-602.
[30]Moacyr Silva, Jr, Alexandre R. Marra, Carlos A. P. Pereira, et al. Bloodstream infection after kidney transplantation:Epidemiology, microbiology, associated risk factors, and outcome[J]. Transplantation 2010,90:581-587.
[31]Foley JM, Paunio M, Lyytikainen O, et al. Bacteremia among kidney transplant recipients:A case-control study of risk factors and shortterm outcomes[J]. Scand J Infect Dis 2000,32:69-73.
[32]Brayman KL, Stephanian E, Matas AJ, et al. Analysis of infectious complications occurring after solid-organ transplantation[J]. Arch Surg 1992,127: 38-47.
[33]Gill JS, Abichandani R, Kausz AT, et al. Mortality after kidney transplant failure:The impact of non-immunologic factors[J]. Kidney Int 2002,62:1875-1883.
[34]Sansalone CV, Maione G, Aseni P, et al. Advantages of short time ureteric stening for prevention of urological complications in kidney transplantation:An 18-year experience[J]. Transplant Proc 2005,37:2511-2515.
[35]L.E. Johnson, E.M.C. D Agata, D.L. Paterson, et al. Pseudomonas aeruginosa bacteremia over a 10-year period:Multidrug resistance and outcomes in transplant recipients[J]. Transpl Infect Dis 2009,11:227-234.
[36]Claire Bellier, Frederic Bert, Francois Durand, et al. Risk factors for enterobacteriaceae bacteremia after liver transplantation[J], Transplant International 2008,21:755-763.
[37]Rabkin DG, Stifelman MD, Birkhoff J, et al. Early catheter removal decreases incidence of urinary tract infections in renal transplant recipients[J]. Transplant Proc 1998,30:4314-4316.
[38]Osman Y, Ali-El-Dein B, Shokeir AA, et al. Routine insertion of ureteral stent in live-donor renal transplantation:Is it worthwhile[J]. Urol 2005,65:867-871.
[39]Wade JJ, Rolando N, Hallar K, et al. Bacterial and fungal infections after liver transplantation:an analysis of 284 patients[J]. Hepatology 1995,21:1328-1366.
[40]Singh N, Gayowski T, Wagener MM, et al. Bloodstream infections in liver transplant recipients receiving tacrolimus[J]. Clin Transplant 1997,11:275-281.
[41]Candel FJ, Grima E, Matesanz M, et al. Bacteremia and septic shock after solid-organ transplantation[J]. Transplant Proc 2005,37(9):4097-4099.
[42]万齐全,肖雪飞,叶启发,等.肝、肾移植受者并发BSIs的死亡危险因素分析[J].中南大学学报(医学版),2012,37(9)：924-927.
[43]Wan Q, Ye Q, Zhou J. Mortality predictors of bloodstream infections in solid-organ transplant recipients[J]. Exp Clin Transplant 2012, Nov 20.
[44]J. Hsu, D. R. Andes, V. Knasinski, et al. Statins are associated with improved outcomes of bloodstream infection in solid-organ transplant recipients[J]. Eur J Clin Microbiol Infect Dis 2009,28:1343-1351.
[45]Maricar F. Malinis, Steven D. Mawhorter, Anil Jain, et al. Staphylococcus aureus bacteremia in solid organ transplant recipients:Evidence for improved survival when compared with nontransplant patients[J]. Transplantation 2012,93:1045-1050.
[46]Silveira FP, Marcos A, Kwak EJ, et al. Bloodstream infections in organ transplant recipients receiving alemtuzumab:No evidence of occurrence of organisms typically associated with profound T cell depletion[J]. J Infect 2006,53:241-247.
[47]Plevak DJ, Southorn PA, Narr BJ. Intensive care unit experience in the Mayo liver transplant program:The first 100 cases[J]. Mayo Clin Proc 1989,64(4): 433-445.
[48]Shieh RM, Chen CL, Wang KL. Respiratory changes and pulmonary complications following orthotopic liver transplantation[J]. Transplant Proc,1992, 24(4):1486-1488.
[49]Torre-Cisneros J, Herrero C, Canas E, et al. High mortality related with Staphylococcus aureus[J]. Eur J Clin Microbiol Infect Dis 2002,21:385-388.
[50]Patterson DL, Singh N, Gayowski T, et al. Rapidly fatal bacteremia due to Staphylococcus aureus producing both enterotoxins A and B in a liver transplant recipient[J]. CLIN INFECT DIS 1997,25:1481-1482.
[51]Wan QQ, Ye QF, Ming YZ, et al. The risk factors for mortality in deceased donor liver transplant recipients with bloodstream infections[J]. Transplant Proc 2013, 45(1):305-307.
[52]Majdi N. Al-Hasan, Raymund R. Razonable, Walter K. Kremers, et al. Impact of gram-negative bloodstream infection on long-term allograft survival after kidney transplantation[J].Transplantation 2011,91:1206-1210.
[53]Danziger-Isakov LA, Sweet S, Delamorena M, et al.Epidemiology of bloodstream infections in the first year after pediatric lung transplantation[J]. Pediatric Infect Dis J 2005,24:324-330.
[54]Rodriguez C, Munoz P, Rodriguez-Creixems M, et al. Bloodstream infections among heart transplant recipients[J]. Transplantation 2006,81:384-391.
[55]Leigh DA. Bacteraemia in patients receiving human cadaveric renal transplants[J]. J Clin Pathol 1971,24:295-299.
[56]Nielsen HE, Korsager B. Bacteremia after renal transplantation[J]. Scand J Infect Dis 1977,9:111-117.
[57]Morduchowicz G, Pitlik SD, Shapira Z, et al. Infections in renal transplant recipients in Israel[J]. Isr J Med Sci 1985,21:791-797.
[58]Lin MF, Lau YJ, Hu BS, et al. Bacteremia in renal transplant recipients: Retrospective analysis of 60 episodes in a teaching hospital[J]. Zhonghua Yi Xue Za Zhi (Taipei) 2001,64:108-114.
[59]Kusne S, Dummer JS, Singh N, et al. Infections after liver transplantation, an analysis of 101 consecutive cases[J]. Medicine 1988,67:132-143.
[60]George DL, Arnow PM, Fox AS, et al. Bacterial infection as a complication of liver transplantation:Epidemiology and risk factors[J]. Review of Infectious Disease 1991,13:387-396.
[61]Singh N, Wagener MM, Obman A, et al. Bacteremias in liver transplant recipients:Shift toward gram-negative bacteria as predominant pathogens[J]. Liver Transpl 2004,10(7):844-849.
[62]肖雪飞,万齐全,叶启发,等.实体器官移植受者BSIs并发感染性休克的危险因素[J].中南大学学报(医学版),2012,37(10)：1050-1053.
[63]D. Kawecki, A. Kwiatkowski, G. Michalak, et al. Etiologic agents of bacteremia in the early period after simultaneous pancreas-kidney transplantation[J]. Transplant Proc 2009,41:3151-3153.
[64]D. Kawecki, A. Chmura, M. Pacholczyk, et al. Etiological agents of bacteremia in the early period after liver transplantation[J]. Transplant Proc 2007,39: 2816-2821.
[65]Husain S, Chan KM, PalmerSM, et al. Bacteremia in lung transplant recipients in the current era[J]. Am J Transplant 2006,6:3000-3007.
[66]Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU[J]. N Engl J Med 2006,355: 2725-2732.
[1]Awad MR, EI-Gamel, Hasleton P, et al. Genotypic variation in the transforming growth factor-betal gene:As sociation with transforming g rowth factor-betal production, fibortic lung disease, and graft fibrosis after lung transplantation[J]. Transplantation 1998,66(8):1014-1020.
[2]Sahoo S, Kang S,Supran S, et al. Tumor necorsis factor genetic polymorphisms correlate with infections after renal transplantation[J]. Transplantaiton 2000,69(5):880-884.
[3]Freeman R B Jr, Tran CL, Mattoli J, et al. Tumor necrosis factor genetic polymorphisms correlate with infections after liver transplantation[J]. Transplantation 1999,67:1005-1010.
[4]顾新伟,赵明,范礼佩,等.TNFa基因多态性在老年人肾移植受者感染中的作用[J].中国医师杂志,2004,6(3)：322-323.
[5]Kimball P, Reid F. Tumor necorsis factor beta gene polymorphisms associated with urinary tract infections after renal transplantaiton[J]. Transplantaiton 2002,73(7):1110-1112.
[6]Leite JL, Manfrinatto JA, Mazzali M, et al. Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients[J]. Transplant Int 2006,19:732-737.
[7]Ducloux D, Deschamps M, Yannaraki M, et al. Relevance of Toll-like receptor-4 polymorphisms in renal transplantation[J]. Kidney Int 2005,67: 2454-2461.
[8]E. Rodrigo, P. Sanchez-Velasco, J.C. Ruiz, et al. Cytokine polymorphisms and risk of infection after kidney transplantation[J]. Transplantation Proc 2007,39: 2219-2221.
[9]Hoffmann TW, Halimi JM, Buchler M, et al. Association between a polymorphism in the IL-12p40 gene and cytomegalovirus reactivation after kidney transplantation[J]. Transplantation 2008,85:1406-1411.
[10][Hoffinann TW, Halimi JM, Buchler M, et al. Association between a polymorphism in the human programmed death-1 (PD-1) gene and cytomegalovirus infection after kidney transplantation[J]. J Med Genet 2010,47:54-58.
[11]羊继平,齐隽,闵志廉,等.肾移植受者细胞因子基因多态性与术后发生感染的关系[J].中华器官移植杂志,2005,26(2)：97-99.
[12]郭义峰,谭建明,李荣宇,等.肾移植受者的细胞因子及其受体单核苷酸多态性与术后感染的相关性[J].中华器官移植杂志,2005,26(9)：531-535.
[13]Wan QQ, Ye QF, Ma Y, et al. Genetic association of interleukin-ip (-511C/T) and its receptor antagonist (86-bpVNTR) gene polymorphism with susceptibility to bacteremia in kidney transplant recipients[J]. Transplant Proc.2012, 44(10):3026-3028.
[14]Alakulppi NS, Kyllonen LE, Salo HME, et al. The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation[J]. Transpl Immunol 2006,16:258-262.
[15]Rosen HR, Lentz JJ, Rose SL, et al. Donor polymorphism of tumor necrosis factor gene:Relationship with variable severity of hepatiits C recurrence after liver transplantaiton[J]. Transplantation 1999,68(12):1898-1902.
[16]Tambur AR, OrtegelJW, Ben-AriZ, et al. Role of cytokine gene polymorphism in hepatitis C recurrence and allograft rejeciton among liver transplant recipients[J]. Transplantation 2001,71(10):1475-1480.
[17]Dennis Eurich, Sabine Boas-Knoop, Marcus Bahra, et al.Role of IL28B polymorphism in the development of hepatitis C virus-Induced hepatocellular carcinoma, graft fibrosis, and posttransplant antiviral therapy[J]. Transplantation 2012, 93:644-649.
[18]Eurich D, Boas-Knoop S, Ruehl M, et al. Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation[J]. Liver Transpl 2011,17:289-298.
[19]Lange CM, Moradpour D, Doehring A, et al. Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection[J]. J Hepatol 2011,55:322-327.
[20]Cisneros E, Banos I, Citores MJ, et al. Increased risk of severe hepatitis C virus recurrence after liver transplantation in patients with a T allele of IL28B rs12979860[J]. Transplantation.2012,94(3):275-280.
[21]Fukuhara T, Taketomi A, Motomura T, et al. Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C[J]. Gastroenterology 2010,139:1577-1585.
[22]Charlton MR, Thompson A, Veldt BJ, et al. Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection[J]. Hepatology 2011,53: 317-324.
[23]Coto-Llerena M, Perez-Del-Pulgar S, Crespo G, et al. Donor and recipient IL28B polymorphisms in HCV-infected patients undergoing antiviral therapy before and after liver transplantation[J]. Am J Transplant 2011,11:1051-1057.
[24]Bertinetto FE, Romagnoli R, Bogantes Hernandez PJ, et al. Role of IL28B polymorphisms in the outcome of liver transplanted HCV infected patients. Abstract for joint 16th international HLA and immunogenetics workshop,26th European Federation of Immunogenetics and 23rd British Society of Histocompatibility and Immunogenetics Conferences [J]. Tissue Antigens 2012,79:481.
[25]Jun Liong Chin, Ross Mac Nicholas, Jennifer Russell,et al. Spontaneous clearance of hepatitis C infection after liver transplantation from IL28B rs 12979860 CC donors[J]. Eur J Gastroenterol Hepatol 2012,24(9):1110-1112.
[26]Li H, Xie HY, Zhou L, et al. Polymorphisms of CCL3L1/CCR5 genes and recurrence of hepatitis B in liver transplant recipients[J]. Hepatobiliary Pancreat Dis Int2011,10(6):593-598.
[27]Ian S. Gourley, David Denofrio, et al. The effect of recipient cytokine gene polymorphism on cardiac transplantation outcome[J]. Human Immunology 2004,65: 248-254.
[28]Kijpittayarit S, Eid AJ, Brown RA, et al. Relationship between toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation[JJ. Clin Infect Dis 2007,44:1315-1320.
[29]Sang-Oh Lee, Robert A. Brown, Seung H. Kang, et al. Toll-like receptor 4 polymorphisms and the risk of gram-negative bacterial infections after liver transplantation[J]. Transplantation 2011,92:690-696.
[30]Sang-Oh Lee, Robert A. Brown, Seung H. Kang, et al. Toll-like receptor 2 polymorphism and gram-positive bacterial infections fter liver transplantationfJ]. Liver Transpl 2011,17:1081-1088.
[31]S.-O. Lee, R.A. Brown, R.R. Razonable. Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients[J]. Transpl Infect Dis 2012, Dec 13.
[32]Zhan-Kui Jin, Cui-Xiang Xu, Pu-Xun Tian, et al. Impact of HLA-G 14-bp polymorphism on acute rejection and cytomegalovirus infection in kidney transplant recipients from northwestern China[J]. Transplant Immunology 2012,27:69-74.
[33]Gourley IS, Denofrio D, Rand W, et al:The effect of recipient cytokine gene polymorphism on cardiac transplantation outcome[J]. Hum Immunol 2004, 65:248-254.
[34]Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases[J]. Clin Infect Dis 2003,37:1496-1505.
[35]Medzhitov R, Janeway C Jr. Innate immunity[J]. N Engl J Med 2000,343: 338-344.
[36]Minchinton RM, Dean MM, Clark TR, et al. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an ustralian blood donor population[J]. Scand J Immunol 2002,56:630-641.
[37]Crosdale DJ, Ollier WE, Thomson W, et al. Mannose-binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids[J]. Eur J Immunogenet 2000,27:111-117.
[38]Turner MW, Hamvas RM. Mannose-binding lectin:Structure, function, genetics and disease associations[J]. Rev Immunogenet 2000,2:305-322.
[39]Madsen HO, Garred P, Thiel S, et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein[J]. J Immunol 1995,155:3013-3020.
[40]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2[J]. Hum Mol Genet 2005,14:1651-1658.
[41]Garred P, Madsen HO, Svejgaard A, et al. Mannose-binding lectin and meningococcal disease[J]. Lancet 1999,354:336, author reply 337.
[42]Worthley DL, Johnson DF, Eisen DP, et al. Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation[J]. Clin Infect Dis 2009,48:410-417.
[43]de Rooij BJ, van Hoek B, Ten Hove WR, et al. Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation[J]. HEPATOLOGY 2010,52:1100-1110.
[44]Bouwman LH, Roos A, Terpstra OT, et al. Mannose-binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation[J]. Gastroenterology 2005,129:408-414.
[45]de Rooij BJ, van der Beek MT, van Hoek B, et al. Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation[J]. J Hepatol 2011,55(4):800-807.
[46]Cervera C, Lozano F, Linares L, et al. Influence of mannose-binding lectin gene polymorphisms on the invasiveness of cytomegalovirus disease after solid organ transplantation[J]. Transplant Proc 2009,41(6):2259-2261.
[47]Verschuren JJ, Roos A, Schaapherder AF, et al. Infectious complications after simultaneous pancreas-kidney transplantation:A role for the lectin pathway of complement activation[J]. Transplantation 2008,85(1):75-80.
[48]Cervera C, Lozano F, Saval N, et al. The influence of innate immunity gene receptors polymorphisms in renal transplant infections[J]. Transplantation 2007, 83(11):1493-500.
[49]Matsushita M, Endo Y, Taira S, et al. A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin[J]. J Biol Chem 1996,271:2448-2454.
[50]Ma YG, Cho MY, Zhao M, et al. Human mannose-binding lectin and 1-ficolin functions specific pattern recognition proteins in the lectin activation pathway of complement[J]. J Biol Chem 2004,279:23307-23312.
[51]Matsushita M, Fujita T. Ficolins and the lectin complement pathway [J]. Immunol Rev 2001,180:78-85.
[52]Thiel S. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins[J]. Mol Immunol 2007,44(16):3875-3888.
[53]Runza VL, Schwaebleb W, Mannel DN. Ficolins:Novel pattern recognition molecules of the innate immune response[J]. lmmuuobiology 2008,213(3-4): 297-306.
[54]Kilpatrick D.C., Fujita T. and Matsushita M. P35, an opsonic lectin of the ficolin family, in human blood from neonates, normal adults, and recurrent miscarriage patients[J]. Immunol Lett 1999,67:109-112.
[55]Taira S., Kodama N., Matsushita M., et al. Opsonic function and concentration of human serum ficolin/P35[J]. Fukushima J Med Sci 2000,46:13-23.
[56]Endo Y, Sato Y, Matsushita M, et al. Cloning and characterization of the human lectin P35 gene and its related gene[J]. Genomics 1996,36:515-521.
[57]Sugimoto R, Yae Y, Akaiwa M, et al. Cloning and characterization of the Hakata antigen, a member of the Ficolin/opsonin p35 lectin family[J]. J Biol Chem 1998,273:20721-20727.
[58]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2[J]. Hum Mol Genet 2005,14:1651-1658.
[59]Haerynck F, Van Steen K, Cattaert T, et al. Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients. Hum Immunol 2012,73(11):1175-1183.
[60]Cedzynski M, Nuytinck L, Atkinson AP, et al. Extremes of L-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene[J]. Clin Exp Immunol.2007,150(1): 99-104.
[61]Ouf EA, Ojurongbe O, Akindele AA, et al. Ficolin-2 levels and FCN2 genetic polymorphisms as a susceptibility factor in schistosomiasis[J]. J Infect Dis 2012,206(4):562-570.
[62]Meijvis SC, Herpers BL, Endeman H, et al. Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on peritoneal dialysis with staphylococcal peritonitis [J]. Nephrol Dial Transplant 2011,26(3):1042-1045.
[63]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns[J]. Mol Immunol 2008,45:2508-2520.
[64]Munthe-Fog L, Hummelshoj T, Hansen BE, et al. The impact of FCN2 polymorphisms and haplotypes on the Ficolin-2 serum levels[J]. Scand J Immunol 2007,65:383-392.
[65]Atkinson AP, Cedzynski M, Szemraj J, et al. L-ficolin in children with recurrent respiratory infections [J]. Clin Exp Immunol 2004,138:517-520.
[66]Chapman SJ, Vannberg FO, Khor CC, et al. Functional polymorphisms in the FCN2 gene are not associated with invasive pneumococcal disease[J]. Mol Immunol 2007,44:3267-3270.
[67]Ruskamp JM, Hoekstra MO, Postma DS, et al. Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children[J]. Clin Exp Immunol 2009,155:433-440.
[68]Faik I, Oyedeji SI, Idris Z, et al. Ficolin-2 levels and genetic polymorphisms of FCN2 in malaria[J]. Hum Immunol 2011,72:74-79.
[69]Messias-Reason I, Kremsner PG, Kun JF. Functional haplotypes that produce normal ficolin-2 levels protect against clinical leprosy[J]. J Infect Dis 2009, 199:801-804.
[70]Messias-Reason IJ, Schafranski MD, Kremsner PG, et al. Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease[J]. Clin Exp Immunol 2009,157:395-399.
[71]Hoang TV, Toan NL, Song le H, et al. Ficolin-2 Levels and FCN2 Haplotypes Influence Hepatitis B Infection Outcome in Vietnamese Patients[J]. PLoS One.2011,6(11):e28113.
[72]Liu J, Ali MA, Shi Y, et al. Specifically binding of L-ficolin to N-glycans of HCV envelope glycoproteins E1 and E2 leads to complement activation[J]. Cell Mol Immunol 2009,6:235-244.
[73]Amal Assaf, Tong Van Hoang, Imad Faik, et al. Genetic Evidence of Functional Ficolin-2 Haplotype as Susceptibility Factor in Cutaneous Leishmaniasis[J]. PLoS One.2012,7(3):e34113.
[74]Roos A, Rastaldi MP, Calvaresi N, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease[J]. J AM SOC NEPHROL 2006,17:1724-1734.
[75]Damman J, Kok JL, Snieder H, et al. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation[J]. Mol Immunol.2012,50(1-2):1-8.
[2]Wagener MM, Yu VL. Bacteremia in transplant recipients:a prospective study of demographics, etiologic agents, risk factors and outcomes[J]. Am J Infect Control 1992,20:239-247.
[3]A. Morenoa, C. Cerveraa, J. Gavald, et al. Bloodstream infections among transplant recipients:results of a nationwide surveillance in Spain[J]. Am J Transplant 2007,7:2579-2586.
[4]Wade JJ, Rolando N, Hayllar K, et al. Bacterial and fungal infections after liver transplantation:an analysis of 284 patients[J]. Hepatology 1995,21:1328-1336.
[5]Singh N, Gayowski T, Wagener MM, et al. Predictors and outcome of early-versus late-onset major bacterial infections in liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression[J]. Eur J Clin Microbiol Infect Dis 1997,16:821-826.
[6]Singh N, Wagener MM, Obman A, et al. Bacteremias in liver transplant recipients:shift toward gram-negative bacteria as predominant pathogens[J]. Liver Transpl 2004,10:844-849.
[7]Taku Iida, Toshimi Kaido, Shintaro Yagi, et al. Posttransplant bacteremia in adult living donor liver transplant recipients [J]. Liver Transpl 2010,16:1379-1385.
[8]Rabkin DG, Stifelman MD, Birkhoff J, et al. Early catheter removal decreases incidence of urinary tract infections in renal transplant recipients[J]. Transplant Proc 1998,30:4314-4316.
[9]Osman Y, Ali-El-Dein B, Shokeir AA, et al. Routine insertion of ureteral stent in live-donor renal transplantation:Is it worthwhile[J]. Urol 2005,65:867-871.
[10]Candel FJ, Grima E, Matesanz M, et al. Bacteremia and septic shock after solid-organ transplantation[J]. Transplant Proc 2005,37:4097-4099.
[11]J. Hsu, D. R. Andes, V. Knasinski, et al. Statins are associated with improved outcomes of bloodstream infection in solid-organ transplant recipients[J]. Eur J Clin Microbiol Infect Dis 2009,28:1343-1351.
[12]Maricar F. Malinis, Steven D. Mawhorter, Anil Jain, et al. Staphylococcus aureus bacteremia in solid organ transplant recipients:Evidence for improved survival when compared with nontransplant patients[J]. Transplantation 2012,93:1045-1050.
[13]Weinstein MP, Towns ML, Quartey SM, et al. The clinical of positive blood cultures in the 1990s:A prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults[J]. Clin Infect Dis 1997,24(4):584-602.
[14]Singh N, Paterson DL, Gayowski T, et al. Predicting bacteremia and bacteremic mortality in liver transplant recipients[J]. Liver Transpl 2000,6:54-61.
[15]Frederic Bert, Beatrice Larroque, Catherine Paugam-Burtz, et al:Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients:An analysis of 259 episodes[J]. Liver Transpl 2010,16:393-401.
[16]Palmer SM, Alexander BD, Sanders LL, et al. Significance of blood stream infection after lung transplantation:Analysis in 176 consecutive patients[J]. Transplant 2000,69:2360-2366.
[17]Silveira FP, Marcos A, Kwak EJ, et al. Bloodstream infections in organ transplant recipients receiving alemtuzumab:No evidence of occurrence of organisms typically associated with profound T cell depletion[J]. J Infect 2006,53:241-247.
[18]Plevak DJ, Southorn PA, Narr BJ. Intensive care unit experience in the Mayo liver transplant program:the first 100 cases[J]. Mayo Clin Proc 1989,64: 433-445.
[19]Shieh RM, Chen CL, Wang KL. Respiratory changes and pulmonary complications following orthotopic liver transplantation[J].Transplant Proc 1992,24: 1486-1488.
[20]J. Torre-Cisneros, C. Herrero, E. Canas, et al:High mortality related with staphylococcus aureus bacteremia after liver transplantation[J]. Eur J Clin Microbiol Infect Dis 2002,21:385-388.
[21]Patterson DL, Singh N, Gayowski T, et al. Rapidly fatal bacteremia due to Staphylococcus aureus producing both enterotoxins A and B in a liver transplant recipient[J]. Clinical Infectious Diseases 1997,25:1481-1482.
[22]Husain S, Tollemar J, Dominguez EA, et al. Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients:Prospective, multicenter, case-controlled study[J]. Transplantation 2003,75:2023-2029.
[23]Shi SH, Kong HS, Xu J, et al. Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients[J]. Transplant Infect Dis 2009,11:405-412.
[24]Moacyr Silva, Jr, Alexandre R. Marra, Carlos A. P. Pereira, et al. Bloodstream infection after kidney transplantation:Epidemiology, microbiology, associated risk factors, and outcome[J]. Transplantation 2010,90:581-587.
[25]Majdi N. Al-Hasan, Raymund R. Razonable, Walter K. Kremers, et al. Impact of gram-negative bloodstream infection on long-term allograft survival after kidney transplantation[J].Transplantation 2011,91:1206-1210.
[26]Danziger-Isakov LA, Sweet S, Delamorena M, et al. Epidemiology of bloodstream infections in the first year after pediatric lung transplantation[J]. Pediatric Infect Dis J 2005,24:324-330.
[27]Rodriguez C, Munoz P, Rodriguez-Creixems M, et al. Bloodstream infections among heart transplant recipients[J]. Transplantation 2006,81:384-391.
[28]Akhter K, Timpone J, Matsumoto C, et al. Six-month incidence of bloodstream infections in intestinal transplant patients[J]. Transpl Infect Dis 2012, 14(3):242-247.
[29]McClean K, Kneteman N, Taylor G. Comparative risk of bloodstream infection in organ transplant recipients[J]. Infect Control Hosp Epidemiol 1994,15(9): 582-584.
[30]Moreno A, Mensa J, Almela M, et al.138 Episodes of bacteremia or fungemia in patients with solid organ (renal or hepatic) transplantation[J]. Med Clin (Bare) 1994,103(5):161-164.
[31]Sang-Oh Lee, Seung H. Kang, Rima C. Abdel-Massih, et al. Spectrum of early-onset and late-onset bacteremias after liver transplantation:Implications for management[J]. Liver Transpl 2011,17(6):733-741.
[32]Linares, J.F. Garcla-Goez, C. Cervera, et al. Early bacteremia after solid organ transplantation[J]. Transplantation Proc 2009,41(6):2262-2264.
[33]Hashimoto M, Sugawara Y, Tamura S, et al. Bloodstream infection after living donor liver transplantation[J]. Scand J Infect Dis 2008,40:509-516.
[34]Ron-Bin Hsu, Chung-I Chang, Chi-Tai Fang, et al. Bloodstream infection in heart transplant recipients:12-year experience at a university hospital in Taiwan[J]. EUR J CARDIO-THORAC 2011,40:1362-1367.
[35]Diana F. Florescu, Fang Qiu, Alan N. Langnas, et al. Bloodstream infections during the first year after pediatric small bowel transplantation[J]. Pediatr Infect Dis J 2012,31:700-704.
[36]Sigurdsson L, Reyes J, Kocoshis SA, et al. Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease[J]. Transplantation 2000,70:302-305.
[37]Garner JS, Jarvis WR, Emori TG, et al. CDC definitions of nosocomial infections[J]. Am J Infect Control 1988,16:128-140.
[38]Levry MM, Fink MP, Marshall JC, et al, for the international sepsis definitions conference.2001 SCCM/ESICM/ACCP/ATS/SIS International sepsis definition conference[J]. Intensive Care Med 2003,29:530-538.
[39]秦文,张剑,李茜,等.ICU获得性血流感染致病菌的临床分析[J].山东大学学报(医学版),2007,45(3)：265-268.
[40]Karunakaran R, Raja NS, Quek KF, et al.Evaluation of the routine use of the anaerobic bottle when using the BACTEC blood culture system[J]. J Microbiol Immunol Infect 2007,40(5):445-449.
[41]Leigh DA. Bacteraemia in patients receiving human cadaveric renal transplants[J]. J Clin Pathol 1971,24:295-299.
[42]Nielsen HE, Korsager B. Bacteremia after renal transplantation[J]. Scand J Infect Dis 1977,9:111-117.
[43]Morduchowicz G, Pitlik SD, Shapira Z, et al. Infections in renal transplant recipients in Israel[J]. Isr J Med Sci 1985,21:791-797.
[44]Lin MF, Lau YJ, Hu BS, et al. Bacteremia in renal transplant recipients: Retrospective analysis of 60 episodes in a teaching hospital[J]. Zhonghua Yi Xue Za Zhi (Taipei) 2001,64:108-114.
[45]Kusne S, Dummer JS, Singh N, et al. Infections after liver transplantation, an analysis of 101 consecutive cases[J]. Medicine 1988,67:132-143.
[46]George DL, Arnow PM, Fox AS, et al. Bacterial infection as a complication of liver transplantation:Epidemiology and risk factors[J]. Review of Infectious Disease 1991,13:387-396.
[47]张卓然,倪语星.临床微生物学和微生物检验[M].北京：人民卫生出版社,2003,3：503-505.
[48]刘剑荣,张勇,陈玲,等.280例血培养阳性标本细菌分布及耐药性分析[J].检验医学与临床,2009,6(4)：279-280.
[49]Leite JL, Manfrinatto JA, Mazzali M, et al. Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients[J]. Transplant Int 2006,19:732-737.
[50]Ducloux D, Deschamps M, Yannaraki M, et al. Relevance of Toll-like receptor-4 polymorphisms in renal transplantation[J]. Kidney Int 2005,67: 2454-2461.
[51]Kimball P, Reid F. Tumor necrosis factor gene polymorphisms associated with urinary tract infections after renal transplantation[J]. Transplantation 2002,73: 1110-1112.
[52]Sahoo S, Kang S, Supran S, et al. Tumor necrosis factor genetic polymorphisms correlate with infections after renal transplantation[J]. Transplantation 2000,69:880-884.
[53]E. Rodrigo, P. Sanchez-Velasco, J.C. Ruiz, et al. Cytokine polymorphisms and risk of infection after kidney transplantation[J]. Transplantation Proc 2007,39: 2219-2221.
[54]郭义峰,谭建明,李荣宇,等.肾移植受者的细胞因子及其受体单核苷酸多态性与术后感染的相关性[J].中华器官移植杂志,2005,26(9)：531-535.
[55]顾新伟,赵明,范礼佩,等.TNFa基因多态性在老年人肾移植受者感染中的作用[J].中国医师杂志,2004,6(3)：322-323.
[56]羊继平,齐隽,闵志廉,等.肾移植受者细胞因子基因多态性与术后发生感染的关系[J].中华器官移植杂志,2005,26(2)：97-99.
[57]Alakulppi NS, Kyllonen LE, Salo HME, et al. The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation[J]. Transpl Immunol 2006,16:258-262.
[58]McClean K, Kneteman N, Taylor G. Comparative risk of bloodstream infection in organ transplant recipients[J]. Infect Control Hosp Epidemiol 1994,15: 582-584.
[59]Moreno A, Mensa J, Almela M, et al.138 Episodes of bacteremia or fungemia in patients with solid organ (renal or hepatic) transplantation[J]. Med Clin (Bare) 1994,103:161-164.
[60]Wagener MM, Yu VL. Bacteremia in transplant recipients:a prospective study of demographics, etiologic agents, risk factors and outcomes[J]. Am J Infect Control 1992,20:239-247.
[61]Jason W. Chi en, Michael J. Boeckh, John A. Hansen, et al. Lipopolysaccharide binding protein promoter variants influence the risk for gram-negative bacteremia and mortality after allogeneic hematopoietic cell transplantation[J]. Blood 2008,111:2462-2469.
[62]Mensah Nana Yaa, Peterlongo Paolo, Steinherz Peter, et al. Toll-Like receptor 4 polymorphisms and risk of gram-negative bacteremia after allogeneic stem cell transplantation. A prospective pilot study[J], Biol Blood Marrow Transplant 2009, 15:1130-1133.
[63]Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases[J]. Clin Infect Dis 2003,37:1496-1505.
[64]Medzhitov R, Janeway C Jr. Innate immunity[J]. N Engl J Med 2000,343: 338-344.
[65]Minchinton RM, Dean MM, Clark TR, et al. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an ustralian blood donor population[J]. Scand J Immunol 2002,56:630-641.
[66]Crosdale DJ, Ollier WE, Thomson W, et al. Mannose-binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids[J]. Eur J Immunogenet 2000,27:111-117.
[67]Turner MW, Hamvas RM. Mannose-binding lectin:structure, function, genetics and disease associations[J]. Rev Immunogenet 2000,2:305-322.
[68]Madsen HO, Garred P, Thiel S, et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein[J]. J Immunol 1995,155:3013-3020.
[69]Garred P, Madsen HO, Svejgaard A, et al. Mannose-binding lectin and meningococcal disease[J]. Lancet 1999,354:336, author reply 337.
[70]Worthley DL, Johnson DF, Eisen DP, et al. Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation[J]. Clin Infect Dis 2009,48:410-417.
[71]de Rooij BJ, van Hoek B, Ten Hove WR, et al. Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation[J]. HEPATOLOGY 2010,52:1100-1110.
[72]Bouwman LH, Roos A, Terpstra OT, et al. Mannose-binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation[J]. Gastroenterology 2005,129:408-414.
[73]de Rooij BJ, van der Beek MT, van Hoek B, et al. Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation[J]. J Hepatol 2011,55(4):800-807.
[74]Cervera C, Lozano F, Linares L, et al. Influence of mannose-binding lectin gene polymorphisms on the invasiveness of cytomegalovirus disease after solid organ transplantation[J]. Transplant Proc 2009,41(6):2259-2261.
[75]Verschuren JJ, Roos A, Schaapherder AF, et al. Infectious complications after simultaneous pancreas-kidney transplantation:A role for the lectin pathway of complement activation[J]. Transplantation 2008,85(1):75-80.
[76]Cervera C, Lozano F, Saval N, et al. The influence of innate immunity gene receptors polymorphisms in renal transplant infections[J]. Transplantation 2007, 83(11):1493-1500.
[77]Matsushita M, Endo Y, Taira S, et al. A novel human serum lectin with collagen-and fibrinogen-like domains that functions as an opsonin[J]. J Biol Chem 1996,271:2448-2454.
[78]Ma YG, Cho MY, Zhao M, et al. Human mannose-binding lectin and 1-ficolin functions specific pattern recognition proteins in the lectin activation pathway of complement[J]. J Biol Chem 2004,279:23307-23312.
[79]Matsushita M, Fujita T. Ficolins and the lectin complement pathway[J]. Immunol Rev 2001,180:78-85.
[80]Thiel S. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins[J]. Mol Immunol 2007,44(16):3875-3888.
[81]Runza VL, Schwaebleb W, Mannel DN. Ficolins:Novel pattern recognition molecules of the innate immune response[J].1 mmuuobiology 2008,213(3-4): 297-306.
[82]Kilpatrick D.C., Fujita T. and Matsushita M. P35, an opsonic lectin of the ficolin family, in human blood from neonates, normal adults, and recurrent miscarriage patients[J]. Immunol Lett 1999,67:109-112.
[83]Taira S., Kodama N., Matsushita M., et al. Opsonic function and concentration of human serum ficolin/P35[J]. Fukushima J Med Sci 2000,46:13-23.
[84]Endo Y, Sato Y, Matsushita M, et al. Cloning and characterization of the human lectin P35 gene and its related gene[J]. Genomics 1996,36:515-521.
[85]Sugimoto R, Yae Y, Akaiwa M, et al.Cloning and characterization of the Hakata antigen, a member of the Ficolin/opsonin p35 lectin family[J]. J Biol Chem 1998,273:20721-20727.
[86]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2[J]. Hum Mol Genet 2005,14:1651-1658.
[87]Haerynck F, Van Steen K, Cattaert T, et al. Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients[J]. Hum Immunol 2012,73(11):1175-1183.
[88]Cedzynski M, Nuytinck L, Atkinson AP, et al. Extremes of L-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene[J]. Clin Exp Immunol.2007,150(1): 99-104.
[89]Ouf EA, Ojurongbe O, Akindele AA, et al. Ficolin-2 levels and FCN2 genetic polymorphisms as a susceptibility factor in schistosomiasis[J]. J Infect Dis 2012,206(4):562-570.
[90]Meijvis SC, Herpers BL, Endeman H, et al. Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on peritoneal dialysis with staphylococcal peritonitis[J]. Nephrol Dial Transplant 2011,26(3):1042-1045.
[91]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns[J]. Mol Immunol 2008,45:2508-2520.
[92]Munthe-Fog L, Hummelshoj T, Hansen BE, Koch C, et al. The impact of FCN2 polymorphisms and haplotypes on the Ficolin-2 serum levels[J]. Scand J Immunol 2007,65:383-392.
[93]Atkinson AP, Cedzynski M, Szemraj J, et al. L-ficolin in children with recurrent respiratory infections[J]. Clin Exp Immunol 2004,138:517-520.
[94]Chapman SJ, Vannberg FO, Khor CC, et al. Functional polymorphisms in the FCN2 gene are not associated with invasive pneumococcal disease[J]. Mol Immunol 2007,44:3267-3270.
[95]Ruskamp JM, Hoekstra MO, Postma DS, et al. Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children[J]. Clin Exp Immunol 2009,155:433-440.
[96]Faik I, Oyedeji SI, Idris Z, et al. Ficolin-2 levels and genetic polymorphisms of FCN2 in malaria[J]. Hum Immunol 2011,72:74-79.
[97]Messias-Reason I, Kremsner PG, Kun JF. Functional haplotypes that produce normal ficolin-2 levels protect against clinical leprosy[J]. J Infect Dis 2009, 199:801-804.
[98]Messias-Reason IJ, Schafranski MD, Kremsner PG, et al. Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease[J]. Clin Exp Immunol 2009,157:395-399.
[99]Hoang TV, Toan NL, Song le H, et al. Ficolin-2 Levels and FCN2 Haplotypes Influence Hepatitis B Infection Outcome in Vietnamese Patients[J]. PLoS One.2011,6(11):e28113.
[100]Liu J, Ali MA, Shi Y, et al. Specifically binding of L-ficolin to N-glycans of HCV envelope glycoproteins E1 and E2 leads to complement activation[J]. Cell Mol Immunol 2009,6:235-244.
[101]Amal Assaf, Tong Van Hoang, Imad Faik, et al. Genetic evidence of functional ficolin-2 haplotype as susceptibility factor in cutaneous leishmaniasis[J]. PLoS One.2012,7(3):e34113.
[102]Roos A, Rastaldi MP, Calvaresi N, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease[J]. Journal of the American Society of Nephrology 2006,17:1724-1734.
[103]Damman J, Kok JL, Snieder H, et al. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation [J]. Mol Immunol.2012,50(1-2):1-8.
[104]Cseh S, Vera L, Matsushita M, et al. Characterization of the interaction between L-ficolin/p35 and mannan-binding lectin-associated serine proteases-1 and-2[J]. J Im muno 2002,169:5735-5743.
[105]Babel N, Cherepnev G, Kowalenko A, et al. Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants[J]. Kidney Int 2004,66:428-432.
[106]Sainz J, Perez E, Gomez-Lopera S, et al. IL-1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate c-reactive protein level[J]. J Clin Immunol 2008,28(5):473-485.
[107]ZHANG Jian, LI Wei-ning, LIN Hua, et al. Genetic polymorphisms of interleukin-10 gene promoter-592 A/C site with hepatitis B virus infection[J]. J Mod Lab Med 2007,22(3):81-84.
[108]Arend WP, Malyak M, Guthridge CJ, et al. Interleukin-1 receptor antagonist:Role in biology[J]. Annu Rev Immunol 1998,16:27-55.
[109]Surbatovic M, Grujic K, Cikota B, et al. Polymorphisms of genes encoding tumor necrosis factor-alpha, interleukin-10, cluster of differentiation-14 and interleukin-lra in critically ill patients[J]. J Crit Care 2010,25(3):542. el-8.63.
[110]Jacob CO, Fronek Z, Lewis GD, et al. Heritable major histocompatibility complex class Ⅱ-associated production of tumor necrosis factor [alpha]:relevance to genetic predisposition to systemic lupus erythematous[J]. Proc Natl Acad Sci USA 1990,87(3):1233-1237.
[111]Jacob CO. Genetic variability in tumor necrosis factor production: relevance to predisposition to autoimmune diseases[J]. Reg Immunol 1992,4(5): 298-304.
[112]Bernal W, Donaldson P, Wendon J. Proinflammatory cytokine genomic polymorphism and critical illness[M]. In:Yearbook of Intensive Care Medicine. Vincent JL (Ed). Berlin, Springer 1999, pp 10-18.
[113]Watanabe E, Hirasawa H, Oda S, et al. Extremely high interleukin-6 blood levels and outcome in the critically ill are associated with tumor necrosis factor- and interleukin-1-related gene polymorphisms[J]. Crit Care Med 2005,33:89-97.
[114]Shu Q, Fang X, Chen Q, et al. IL-10 polymorphism is associated with increased incidence of severe sepsis[J]. Chin Med J 2003,116:1756-1759.
[115]Gong MN, Thompson BT, Williams PL, et al. Interleukin-10 polymorphism in position-1082 and acute respiratory distress syndrome[J]. Eur Respir J 2006,27:674-681.
[116]Messer G, Spengler U, Jung MC, et al. Polymorphic structure of tumor necrosis factor (TNF) locus:an Ncol polymorphism in the first intron of the TNF-beta gene correlates with a variant amino acid in position 26 and reduced level of TNF-beta production[J]. J Exp Med 1991,173(1):209-219.
[117]Piciot F, Molvig J, Wogensen L, et al. A tumor necrosis factor beta polymorphism in relation to monokine secretion and insulin-dependent diabetes mellitus[J]. Scand J Immunol 1991,33 (1):37-49.
[118]Pociot F, Briant L, Jongeneel CV, et al. Association of tumor necrosis factor (TNF) and class Ⅱ major histocompatibility complex alleles with the secretion of TNF-alpha and TNF-beta by human mononuclear cells:a possible link to insulin-dependent diabetes mellitus[J]. Eur J Immunol 1993,23:224-231.
[119]Riese J, Woerner K, Zimmermann P, et al. Association of a TNFb gene polymorphism with complications after major abdominal operations[J]. Shock 2003, 19:1-4.
[120]Watanabe E, Buchman H, Hirasawa H, et al. Association between lymphotoxin-[alpha] (tumor necrosis factor-[beta]) intron polymorphism and predisposition to severe sepsis is modified by gender and age[J]. Crit Care Med 2010, 38(1):181-193.
[121]Cervera C, Balderramo D, Suarez B, et al. Donor mannose-binding lectin gene polymorphisms influence the outcome of liver transplantation[J]. Liver Transpl 2009,15 (10):1217-1224.
[122]Rantala A, Lajunen T, Juvonen R, et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men[J]. J Infect Dis 2008,198:1247-1253.
[123]Steffensen R, Thiel S, Varming K, et al. Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers[J]. J Immunol Methods 2000,241:33-42.
[124]Neth O, Jack DL, Dodds AW, et al. Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement deposition[J]. Infect Immun 2000,68:688-693.
[125]Petersen KA, Matthiesen F, Agger T, et al. Phase I safety, tolerability, and pharmacokinetic study of recoMBLnant human mannanbinding lectin[J]. J Clin Immunol 2006,26:465-475.
[126]Summerfield JA. Clinical potential of mannose-binding lectin-replacement therapy[J]. Biochem Soc Trans 2003,31:770-773.
[127]Valdimarsson H. Infusion of plasma-derived mannan-binding lectin (MBL) into MBL-deficient humans[J]. Biochem Soc Trans 2003,31:768-769.
[128]Valdimarsson H, Vikingsdottir T, Bang P, et al. Human plasma-derived mannose-binding lectin:a phase I safety and pharmacokinetic study[J]. Scand J Immunol 2004,59:97-102.
[129]Matsushita M, Fujita T. Activation of the classical complement pathway by mannose-binding protein in association with a novel Cls-like serine protease[J]. J Exp Med 1992,176:1497-1502.
[130]Matsushita M, Endo Y, Fujita T. Cutting edge:complement-activating complex of ficolin and mannose-binding lectin-associated serine protease[J]. J Immunol 2000,164:2281-2284.
[131]Petersen, S.V., Thiel, S., Jensenius, J.C. The mannan-binding lectin pathway of complement activation:biology and disease association[J]. Mol Immunol 2001,38:133-149.
[132]Damman J, Kok JL, Snieder H, et al. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation[J]. Mol Immunol.2012,50(1-2):1-8.
[133]Kilpatrick DC, McLintock LA, Allan EK, Copland M, Fujita T, Jordanides NE, et al. No strong relationship between mannan binding lectin or plasma ficolins and chemotherapy-related infections[J]. Clin Exp Immunol 2003,134:279-284.
[134]Schlapbach LJ, Mattmann M, Thiel S, Boillat C, Otth M, Nelle M, et al. Differential role of the lectin pathway of complement activation in susceptibility to neonatal sepsis[J]. Clin Infect Dis 2010,51:153-162.
[135]Atkinson AP, Cedzynski M, Szemraj J, St Swierzko A, Bak-Romaniszyn L, et al. L-ficolin in children with recurrent respiratory infections[J]. Clin Exp Immunol 2004,138:517-520.
[1]Wagener MM, Yu VL. Bacteremia in transplant recipients:A prospective study of demographics, etiologic agents, risk factors and outcomes[J]. Am J Infect Control 1992,20:239-247.
[2]McClean K, Kneteman N, Taylor G. Comparative risk of bloodstream infection in organ transplant recipients[J]. Infect Control Hosp Epidemiol 1994,15: 582-584.
[3]Moreno A, Mensa J, Almela M, et al.138 Episodes of bacteremia or fungemia in patients with solid organ (renal or hepatic) transplantation[J]. Med Clin (Barc) 1994,103:161-164.
[4]Sang-Oh Lee, Seung H. Kang, Rima C. Abdel-Massih, et al. Spectrum of early-onset and late-onset bacteremias after liver transplantation:Implications for management J]. Liver Transpl 2011,17(6):733-741.
[5]L. Linares, J.F. Garcla-Goez, C. Cervera, et al. Early bacteremia after solid organ transplantation[J]. Transplantation Proc 2009,41(6):2262-2264.
[6]Palmer SM, Alexander BD, Sanders LL, et al. Significance of blood stream infection after lung transplantation:Analysis in 176 consecutive patients[J]. Transplant 2000,69:2360-2366.
[7]A. Morenoa, C. Cerveraa, J. Gavald, et al. Bloodstream infections among transplant recipients:results of a nationwide surveillance in Spain[J]. Am J Transplant 2007,7(11):2579-2586.
[8]Kim S, Kim Y, Jun Y, et al. Epidemiology and risk factors for bacteremia in 144 consecutive living-donor liver transplant recipients[J]. Yonsei Med J 2009,50(1): 112-121.
[9]Taku Iida, Toshimi Kaido, Shintaro Yagi, et al. Posttransplant bacteremia in adult living donor liver transplant recipients[J]. Liver Transpl 2010,16:1379-1385.
[10]Hashimoto M, Sugawara Y, Tamura S, et al. Bloodstream infection after living donor liver transplantation[J]. Scand J Infect Dis 2008,40:509-516.
[11]Ron-Bin Hsu, Chung-I Chang, Chi-Tai Fang, et al. Bloodstream infection in heart transplant recipients:12-year experience at a university hospital in Taiwan[J]. EUR J CARDIO-THORAC 2011,40:1362-1367.
[12]Diana F. Florescu, Fang Qiu, Alan N. Langnas, et al. Bloodstream infections during the first year after pediatric small bowel transplantationfJ]. Pediatr Infect Dis J 2012,31:700-704.
[13]Sigurdsson L, Reyes J, Kocoshis SA, et al. Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease[J]. Transplantation 2000,70:302-305.
[14]Akhter K, Timpone J, Matsumoto C, et al. Six-month incidence of bloodstream infections in intestinal transplant patients[J]. Transpl Infect Dis 2012, 14(3):242-247.
[15]Singh N, Paterson DL, Gayowski T, et al. Predicting bacteremia and bacteremic mortality in liver transplant recipients[J]. Liver Transpl 2000,6(1):54-61.
[16]Singh N, Paterson DL, Chang FY, et al. Methicillin-resistant Staphlococcus aureus:The other emerging resistant Gram-positive coccus among liver transplant recipients[J]. Clin Infect Dis 2000,30:332-327.
[17]Bert F, Galdbart J-O, Zarrouk V, et al. Association between Staphylococcus aureus nasal carriage and infection in liver transplant recipients[J]. Clin Infect Dis 2000,31:1295-1299.
[18]Bert F, Bellier C, Lassel L, et al. Risk factors for Staphylococcus aureus infection for liver transplant recipients[J]. Liver Transpl 2005,11:1093-1099.
[19]Frederic Bert, Beatrice Larroque, Catherine Paugam-Burtz, et al. Microbial epidemiology and outcome of bloodstream infections in liver transplant recipients:An analysis of 259 episodes[J]. Liver Transpl 2010,16:393-401.
[20]Bedini A, Codeluppi M, Cocchi S, et al. Gram-positive bloodstream infections in liver transplant recipients:Incidence, risk factors, andimpact on survival[J]. Transplant Proc 2007,39:1947-1949.
[21]Husain S, Tollemar J, Dominguez EA, et al. Changes in the spectrum and risk factors for invasive candidiasis in liver transplant recipients:Prospective, multicenter, case-controlled study[J]. Transplantation 2003,75:2023-2029.
[22]Bellier C, Bert F, Durand F, et al. Risk factors for Enterobacteriaceae bacteremia after liver transplantation[J]. Transpl Int 2008,21:755-763.
[23]Falagas ME, Snydman DR, Griffith J, Werner BG, the Boston Center for Liver Transplantation CMVIG Study Group. Exposure to cytomegalovirus from the donated organ is a risk factor for bacteremia in orthotopic liver transplant recipients[J]. Clin Infect Dis 1996,23:468-474.
[24]Toshimi Kaido, Akira Mori, Yasuhiro Ogura, et al. Pre-and perioperative factors affecting infection after living donor liver Transplantation[J]. Nutrition 2012, 28:1104-1108.
[25]Shi SH, Kong HS, Xu J, et al. Multidrug resistant gram-negative bacilli as predominant bacteremic pathogens in liver transplant recipients[J]. Transplant Infect Dis 2009,11:405-412.
[26]SHI Shao-hua, KONG Hai-shen, JIA Chang-ku, et al. Coagulase-negative staphylococcus and enterococcus aspredominant pathogens in liver transplant recipients with gram-positive coccal bacteremia[J]. Chinese Medical Journal 2010, 123(15):1983-1988.
[27]Saner FH, Olde Damink SWM, Pavlakovic G, et al. Pulmonary and bloodstream infections in adult living donor and cadaveric liver transplant patientsfJ]. Transplantation 2008,85:1564-1568.
[28]K.W. Rhee, S.H. Oh, K.M. Kim, et al. Early bloodstream infection after pediatric living donor living transplantation[J]. Transplant Proc 2012,44:794-796.
[29]Weinstein MP, Towns ML, Quartey SM, et al. The clinical of positive blood cultures in the 1990s:A prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults[J]. Clin Infect Dis 1997,24(4):584-602.
[30]Moacyr Silva, Jr, Alexandre R. Marra, Carlos A. P. Pereira, et al. Bloodstream infection after kidney transplantation:Epidemiology, microbiology, associated risk factors, and outcome[J]. Transplantation 2010,90:581-587.
[31]Foley JM, Paunio M, Lyytikainen O, et al. Bacteremia among kidney transplant recipients:A case-control study of risk factors and shortterm outcomes[J]. Scand J Infect Dis 2000,32:69-73.
[32]Brayman KL, Stephanian E, Matas AJ, et al. Analysis of infectious complications occurring after solid-organ transplantation[J]. Arch Surg 1992,127: 38-47.
[33]Gill JS, Abichandani R, Kausz AT, et al. Mortality after kidney transplant failure:The impact of non-immunologic factors[J]. Kidney Int 2002,62:1875-1883.
[34]Sansalone CV, Maione G, Aseni P, et al. Advantages of short time ureteric stening for prevention of urological complications in kidney transplantation:An 18-year experience[J]. Transplant Proc 2005,37:2511-2515.
[35]L.E. Johnson, E.M.C. D Agata, D.L. Paterson, et al. Pseudomonas aeruginosa bacteremia over a 10-year period:Multidrug resistance and outcomes in transplant recipients[J]. Transpl Infect Dis 2009,11:227-234.
[36]Claire Bellier, Frederic Bert, Francois Durand, et al. Risk factors for enterobacteriaceae bacteremia after liver transplantation[J], Transplant International 2008,21:755-763.
[37]Rabkin DG, Stifelman MD, Birkhoff J, et al. Early catheter removal decreases incidence of urinary tract infections in renal transplant recipients[J]. Transplant Proc 1998,30:4314-4316.
[38]Osman Y, Ali-El-Dein B, Shokeir AA, et al. Routine insertion of ureteral stent in live-donor renal transplantation:Is it worthwhile[J]. Urol 2005,65:867-871.
[39]Wade JJ, Rolando N, Hallar K, et al. Bacterial and fungal infections after liver transplantation:an analysis of 284 patients[J]. Hepatology 1995,21:1328-1366.
[40]Singh N, Gayowski T, Wagener MM, et al. Bloodstream infections in liver transplant recipients receiving tacrolimus[J]. Clin Transplant 1997,11:275-281.
[41]Candel FJ, Grima E, Matesanz M, et al. Bacteremia and septic shock after solid-organ transplantation[J]. Transplant Proc 2005,37(9):4097-4099.
[42]万齐全,肖雪飞,叶启发,等.肝、肾移植受者并发BSIs的死亡危险因素分析[J].中南大学学报(医学版),2012,37(9)：924-927.
[43]Wan Q, Ye Q, Zhou J. Mortality predictors of bloodstream infections in solid-organ transplant recipients[J]. Exp Clin Transplant 2012, Nov 20.
[44]J. Hsu, D. R. Andes, V. Knasinski, et al. Statins are associated with improved outcomes of bloodstream infection in solid-organ transplant recipients[J]. Eur J Clin Microbiol Infect Dis 2009,28:1343-1351.
[45]Maricar F. Malinis, Steven D. Mawhorter, Anil Jain, et al. Staphylococcus aureus bacteremia in solid organ transplant recipients:Evidence for improved survival when compared with nontransplant patients[J]. Transplantation 2012,93:1045-1050.
[46]Silveira FP, Marcos A, Kwak EJ, et al. Bloodstream infections in organ transplant recipients receiving alemtuzumab:No evidence of occurrence of organisms typically associated with profound T cell depletion[J]. J Infect 2006,53:241-247.
[47]Plevak DJ, Southorn PA, Narr BJ. Intensive care unit experience in the Mayo liver transplant program:The first 100 cases[J]. Mayo Clin Proc 1989,64(4): 433-445.
[48]Shieh RM, Chen CL, Wang KL. Respiratory changes and pulmonary complications following orthotopic liver transplantation[J]. Transplant Proc,1992, 24(4):1486-1488.
[49]Torre-Cisneros J, Herrero C, Canas E, et al. High mortality related with Staphylococcus aureus[J]. Eur J Clin Microbiol Infect Dis 2002,21:385-388.
[50]Patterson DL, Singh N, Gayowski T, et al. Rapidly fatal bacteremia due to Staphylococcus aureus producing both enterotoxins A and B in a liver transplant recipient[J]. CLIN INFECT DIS 1997,25:1481-1482.
[51]Wan QQ, Ye QF, Ming YZ, et al. The risk factors for mortality in deceased donor liver transplant recipients with bloodstream infections[J]. Transplant Proc 2013, 45(1):305-307.
[52]Majdi N. Al-Hasan, Raymund R. Razonable, Walter K. Kremers, et al. Impact of gram-negative bloodstream infection on long-term allograft survival after kidney transplantation[J].Transplantation 2011,91:1206-1210.
[53]Danziger-Isakov LA, Sweet S, Delamorena M, et al.Epidemiology of bloodstream infections in the first year after pediatric lung transplantation[J]. Pediatric Infect Dis J 2005,24:324-330.
[54]Rodriguez C, Munoz P, Rodriguez-Creixems M, et al. Bloodstream infections among heart transplant recipients[J]. Transplantation 2006,81:384-391.
[55]Leigh DA. Bacteraemia in patients receiving human cadaveric renal transplants[J]. J Clin Pathol 1971,24:295-299.
[56]Nielsen HE, Korsager B. Bacteremia after renal transplantation[J]. Scand J Infect Dis 1977,9:111-117.
[57]Morduchowicz G, Pitlik SD, Shapira Z, et al. Infections in renal transplant recipients in Israel[J]. Isr J Med Sci 1985,21:791-797.
[58]Lin MF, Lau YJ, Hu BS, et al. Bacteremia in renal transplant recipients: Retrospective analysis of 60 episodes in a teaching hospital[J]. Zhonghua Yi Xue Za Zhi (Taipei) 2001,64:108-114.
[59]Kusne S, Dummer JS, Singh N, et al. Infections after liver transplantation, an analysis of 101 consecutive cases[J]. Medicine 1988,67:132-143.
[60]George DL, Arnow PM, Fox AS, et al. Bacterial infection as a complication of liver transplantation:Epidemiology and risk factors[J]. Review of Infectious Disease 1991,13:387-396.
[61]Singh N, Wagener MM, Obman A, et al. Bacteremias in liver transplant recipients:Shift toward gram-negative bacteria as predominant pathogens[J]. Liver Transpl 2004,10(7):844-849.
[62]肖雪飞,万齐全,叶启发,等.实体器官移植受者BSIs并发感染性休克的危险因素[J].中南大学学报(医学版),2012,37(10)：1050-1053.
[63]D. Kawecki, A. Kwiatkowski, G. Michalak, et al. Etiologic agents of bacteremia in the early period after simultaneous pancreas-kidney transplantation[J]. Transplant Proc 2009,41:3151-3153.
[64]D. Kawecki, A. Chmura, M. Pacholczyk, et al. Etiological agents of bacteremia in the early period after liver transplantation[J]. Transplant Proc 2007,39: 2816-2821.
[65]Husain S, Chan KM, PalmerSM, et al. Bacteremia in lung transplant recipients in the current era[J]. Am J Transplant 2006,6:3000-3007.
[66]Pronovost P, Needham D, Berenholtz S, et al. An intervention to decrease catheter-related bloodstream infections in the ICU[J]. N Engl J Med 2006,355: 2725-2732.
[1]Awad MR, EI-Gamel, Hasleton P, et al. Genotypic variation in the transforming growth factor-betal gene:As sociation with transforming g rowth factor-betal production, fibortic lung disease, and graft fibrosis after lung transplantation[J]. Transplantation 1998,66(8):1014-1020.
[2]Sahoo S, Kang S,Supran S, et al. Tumor necorsis factor genetic polymorphisms correlate with infections after renal transplantation[J]. Transplantaiton 2000,69(5):880-884.
[3]Freeman R B Jr, Tran CL, Mattoli J, et al. Tumor necrosis factor genetic polymorphisms correlate with infections after liver transplantation[J]. Transplantation 1999,67:1005-1010.
[4]顾新伟,赵明,范礼佩,等.TNFa基因多态性在老年人肾移植受者感染中的作用[J].中国医师杂志,2004,6(3)：322-323.
[5]Kimball P, Reid F. Tumor necorsis factor beta gene polymorphisms associated with urinary tract infections after renal transplantaiton[J]. Transplantaiton 2002,73(7):1110-1112.
[6]Leite JL, Manfrinatto JA, Mazzali M, et al. Polymorphisms at exon 4 of p53 and the susceptibility to herpesvirus types 6 and 1 infection in renal transplant recipients[J]. Transplant Int 2006,19:732-737.
[7]Ducloux D, Deschamps M, Yannaraki M, et al. Relevance of Toll-like receptor-4 polymorphisms in renal transplantation[J]. Kidney Int 2005,67: 2454-2461.
[8]E. Rodrigo, P. Sanchez-Velasco, J.C. Ruiz, et al. Cytokine polymorphisms and risk of infection after kidney transplantation[J]. Transplantation Proc 2007,39: 2219-2221.
[9]Hoffmann TW, Halimi JM, Buchler M, et al. Association between a polymorphism in the IL-12p40 gene and cytomegalovirus reactivation after kidney transplantation[J]. Transplantation 2008,85:1406-1411.
[10][Hoffinann TW, Halimi JM, Buchler M, et al. Association between a polymorphism in the human programmed death-1 (PD-1) gene and cytomegalovirus infection after kidney transplantation[J]. J Med Genet 2010,47:54-58.
[11]羊继平,齐隽,闵志廉,等.肾移植受者细胞因子基因多态性与术后发生感染的关系[J].中华器官移植杂志,2005,26(2)：97-99.
[12]郭义峰,谭建明,李荣宇,等.肾移植受者的细胞因子及其受体单核苷酸多态性与术后感染的相关性[J].中华器官移植杂志,2005,26(9)：531-535.
[13]Wan QQ, Ye QF, Ma Y, et al. Genetic association of interleukin-ip (-511C/T) and its receptor antagonist (86-bpVNTR) gene polymorphism with susceptibility to bacteremia in kidney transplant recipients[J]. Transplant Proc.2012, 44(10):3026-3028.
[14]Alakulppi NS, Kyllonen LE, Salo HME, et al. The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation[J]. Transpl Immunol 2006,16:258-262.
[15]Rosen HR, Lentz JJ, Rose SL, et al. Donor polymorphism of tumor necrosis factor gene:Relationship with variable severity of hepatiits C recurrence after liver transplantaiton[J]. Transplantation 1999,68(12):1898-1902.
[16]Tambur AR, OrtegelJW, Ben-AriZ, et al. Role of cytokine gene polymorphism in hepatitis C recurrence and allograft rejeciton among liver transplant recipients[J]. Transplantation 2001,71(10):1475-1480.
[17]Dennis Eurich, Sabine Boas-Knoop, Marcus Bahra, et al.Role of IL28B polymorphism in the development of hepatitis C virus-Induced hepatocellular carcinoma, graft fibrosis, and posttransplant antiviral therapy[J]. Transplantation 2012, 93:644-649.
[18]Eurich D, Boas-Knoop S, Ruehl M, et al. Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation[J]. Liver Transpl 2011,17:289-298.
[19]Lange CM, Moradpour D, Doehring A, et al. Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection[J]. J Hepatol 2011,55:322-327.
[20]Cisneros E, Banos I, Citores MJ, et al. Increased risk of severe hepatitis C virus recurrence after liver transplantation in patients with a T allele of IL28B rs12979860[J]. Transplantation.2012,94(3):275-280.
[21]Fukuhara T, Taketomi A, Motomura T, et al. Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C[J]. Gastroenterology 2010,139:1577-1585.
[22]Charlton MR, Thompson A, Veldt BJ, et al. Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection[J]. Hepatology 2011,53: 317-324.
[23]Coto-Llerena M, Perez-Del-Pulgar S, Crespo G, et al. Donor and recipient IL28B polymorphisms in HCV-infected patients undergoing antiviral therapy before and after liver transplantation[J]. Am J Transplant 2011,11:1051-1057.
[24]Bertinetto FE, Romagnoli R, Bogantes Hernandez PJ, et al. Role of IL28B polymorphisms in the outcome of liver transplanted HCV infected patients. Abstract for joint 16th international HLA and immunogenetics workshop,26th European Federation of Immunogenetics and 23rd British Society of Histocompatibility and Immunogenetics Conferences [J]. Tissue Antigens 2012,79:481.
[25]Jun Liong Chin, Ross Mac Nicholas, Jennifer Russell,et al. Spontaneous clearance of hepatitis C infection after liver transplantation from IL28B rs 12979860 CC donors[J]. Eur J Gastroenterol Hepatol 2012,24(9):1110-1112.
[26]Li H, Xie HY, Zhou L, et al. Polymorphisms of CCL3L1/CCR5 genes and recurrence of hepatitis B in liver transplant recipients[J]. Hepatobiliary Pancreat Dis Int2011,10(6):593-598.
[27]Ian S. Gourley, David Denofrio, et al. The effect of recipient cytokine gene polymorphism on cardiac transplantation outcome[J]. Human Immunology 2004,65: 248-254.
[28]Kijpittayarit S, Eid AJ, Brown RA, et al. Relationship between toll-like receptor 2 polymorphism and cytomegalovirus disease after liver transplantation[JJ. Clin Infect Dis 2007,44:1315-1320.
[29]Sang-Oh Lee, Robert A. Brown, Seung H. Kang, et al. Toll-like receptor 4 polymorphisms and the risk of gram-negative bacterial infections after liver transplantation[J]. Transplantation 2011,92:690-696.
[30]Sang-Oh Lee, Robert A. Brown, Seung H. Kang, et al. Toll-like receptor 2 polymorphism and gram-positive bacterial infections fter liver transplantationfJ]. Liver Transpl 2011,17:1081-1088.
[31]S.-O. Lee, R.A. Brown, R.R. Razonable. Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients[J]. Transpl Infect Dis 2012, Dec 13.
[32]Zhan-Kui Jin, Cui-Xiang Xu, Pu-Xun Tian, et al. Impact of HLA-G 14-bp polymorphism on acute rejection and cytomegalovirus infection in kidney transplant recipients from northwestern China[J]. Transplant Immunology 2012,27:69-74.
[33]Gourley IS, Denofrio D, Rand W, et al:The effect of recipient cytokine gene polymorphism on cardiac transplantation outcome[J]. Hum Immunol 2004, 65:248-254.
[34]Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases[J]. Clin Infect Dis 2003,37:1496-1505.
[35]Medzhitov R, Janeway C Jr. Innate immunity[J]. N Engl J Med 2000,343: 338-344.
[36]Minchinton RM, Dean MM, Clark TR, et al. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an ustralian blood donor population[J]. Scand J Immunol 2002,56:630-641.
[37]Crosdale DJ, Ollier WE, Thomson W, et al. Mannose-binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids[J]. Eur J Immunogenet 2000,27:111-117.
[38]Turner MW, Hamvas RM. Mannose-binding lectin:Structure, function, genetics and disease associations[J]. Rev Immunogenet 2000,2:305-322.
[39]Madsen HO, Garred P, Thiel S, et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein[J]. J Immunol 1995,155:3013-3020.
[40]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2[J]. Hum Mol Genet 2005,14:1651-1658.
[41]Garred P, Madsen HO, Svejgaard A, et al. Mannose-binding lectin and meningococcal disease[J]. Lancet 1999,354:336, author reply 337.
[42]Worthley DL, Johnson DF, Eisen DP, et al. Donor mannose-binding lectin deficiency increases the likelihood of clinically significant infection after liver transplantation[J]. Clin Infect Dis 2009,48:410-417.
[43]de Rooij BJ, van Hoek B, Ten Hove WR, et al. Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation[J]. HEPATOLOGY 2010,52:1100-1110.
[44]Bouwman LH, Roos A, Terpstra OT, et al. Mannose-binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation[J]. Gastroenterology 2005,129:408-414.
[45]de Rooij BJ, van der Beek MT, van Hoek B, et al. Mannose-binding lectin and Ficolin-2 gene polymorphisms predispose to cytomegalovirus (re)infection after orthotopic liver transplantation[J]. J Hepatol 2011,55(4):800-807.
[46]Cervera C, Lozano F, Linares L, et al. Influence of mannose-binding lectin gene polymorphisms on the invasiveness of cytomegalovirus disease after solid organ transplantation[J]. Transplant Proc 2009,41(6):2259-2261.
[47]Verschuren JJ, Roos A, Schaapherder AF, et al. Infectious complications after simultaneous pancreas-kidney transplantation:A role for the lectin pathway of complement activation[J]. Transplantation 2008,85(1):75-80.
[48]Cervera C, Lozano F, Saval N, et al. The influence of innate immunity gene receptors polymorphisms in renal transplant infections[J]. Transplantation 2007, 83(11):1493-500.
[49]Matsushita M, Endo Y, Taira S, et al. A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin[J]. J Biol Chem 1996,271:2448-2454.
[50]Ma YG, Cho MY, Zhao M, et al. Human mannose-binding lectin and 1-ficolin functions specific pattern recognition proteins in the lectin activation pathway of complement[J]. J Biol Chem 2004,279:23307-23312.
[51]Matsushita M, Fujita T. Ficolins and the lectin complement pathway [J]. Immunol Rev 2001,180:78-85.
[52]Thiel S. Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins[J]. Mol Immunol 2007,44(16):3875-3888.
[53]Runza VL, Schwaebleb W, Mannel DN. Ficolins:Novel pattern recognition molecules of the innate immune response[J]. lmmuuobiology 2008,213(3-4): 297-306.
[54]Kilpatrick D.C., Fujita T. and Matsushita M. P35, an opsonic lectin of the ficolin family, in human blood from neonates, normal adults, and recurrent miscarriage patients[J]. Immunol Lett 1999,67:109-112.
[55]Taira S., Kodama N., Matsushita M., et al. Opsonic function and concentration of human serum ficolin/P35[J]. Fukushima J Med Sci 2000,46:13-23.
[56]Endo Y, Sato Y, Matsushita M, et al. Cloning and characterization of the human lectin P35 gene and its related gene[J]. Genomics 1996,36:515-521.
[57]Sugimoto R, Yae Y, Akaiwa M, et al. Cloning and characterization of the Hakata antigen, a member of the Ficolin/opsonin p35 lectin family[J]. J Biol Chem 1998,273:20721-20727.
[58]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2[J]. Hum Mol Genet 2005,14:1651-1658.
[59]Haerynck F, Van Steen K, Cattaert T, et al. Polymorphisms in the lectin pathway genes as a possible cause of early chronic Pseudomonas aeruginosa colonization in cystic fibrosis patients. Hum Immunol 2012,73(11):1175-1183.
[60]Cedzynski M, Nuytinck L, Atkinson AP, et al. Extremes of L-ficolin concentration in children with recurrent infections are associated with single nucleotide polymorphisms in the FCN2 gene[J]. Clin Exp Immunol.2007,150(1): 99-104.
[61]Ouf EA, Ojurongbe O, Akindele AA, et al. Ficolin-2 levels and FCN2 genetic polymorphisms as a susceptibility factor in schistosomiasis[J]. J Infect Dis 2012,206(4):562-570.
[62]Meijvis SC, Herpers BL, Endeman H, et al. Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on peritoneal dialysis with staphylococcal peritonitis [J]. Nephrol Dial Transplant 2011,26(3):1042-1045.
[63]Hummelshoj T, Munthe-Fog L, Madsen HO, et al. Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns[J]. Mol Immunol 2008,45:2508-2520.
[64]Munthe-Fog L, Hummelshoj T, Hansen BE, et al. The impact of FCN2 polymorphisms and haplotypes on the Ficolin-2 serum levels[J]. Scand J Immunol 2007,65:383-392.
[65]Atkinson AP, Cedzynski M, Szemraj J, et al. L-ficolin in children with recurrent respiratory infections [J]. Clin Exp Immunol 2004,138:517-520.
[66]Chapman SJ, Vannberg FO, Khor CC, et al. Functional polymorphisms in the FCN2 gene are not associated with invasive pneumococcal disease[J]. Mol Immunol 2007,44:3267-3270.
[67]Ruskamp JM, Hoekstra MO, Postma DS, et al. Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children[J]. Clin Exp Immunol 2009,155:433-440.
[68]Faik I, Oyedeji SI, Idris Z, et al. Ficolin-2 levels and genetic polymorphisms of FCN2 in malaria[J]. Hum Immunol 2011,72:74-79.
[69]Messias-Reason I, Kremsner PG, Kun JF. Functional haplotypes that produce normal ficolin-2 levels protect against clinical leprosy[J]. J Infect Dis 2009, 199:801-804.
[70]Messias-Reason IJ, Schafranski MD, Kremsner PG, et al. Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease[J]. Clin Exp Immunol 2009,157:395-399.
[71]Hoang TV, Toan NL, Song le H, et al. Ficolin-2 Levels and FCN2 Haplotypes Influence Hepatitis B Infection Outcome in Vietnamese Patients[J]. PLoS One.2011,6(11):e28113.
[72]Liu J, Ali MA, Shi Y, et al. Specifically binding of L-ficolin to N-glycans of HCV envelope glycoproteins E1 and E2 leads to complement activation[J]. Cell Mol Immunol 2009,6:235-244.
[73]Amal Assaf, Tong Van Hoang, Imad Faik, et al. Genetic Evidence of Functional Ficolin-2 Haplotype as Susceptibility Factor in Cutaneous Leishmaniasis[J]. PLoS One.2012,7(3):e34113.
[74]Roos A, Rastaldi MP, Calvaresi N, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease[J]. J AM SOC NEPHROL 2006,17:1724-1734.
[75]Damman J, Kok JL, Snieder H, et al. Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation[J]. Mol Immunol.2012,50(1-2):1-8.