PRA、HLA抗体及MICA监测肾移植术后排斥反应的研究
摘要
群体反应性抗体(panel reactive antibodies, PRA)是一种IgG类型的机体内体液性免疫抗体,即群体反应性抗HLA-IgG抗体,主要针对人类HLA抗原,特异性强。是否成为外科领域组织器官移植术前筛选致敏受者的重要指标,与移植排斥反应和存活率是否密切相关现已成为研究就热点。由于人类白细胞抗原的多样性,相应的抗体种类也是多种多样的。HLA供受者配型良好的排斥发生和促进移植肾功能的恢复较好,并可降低移植受者的致敏性,可以使移植肾术后长期存活。有研究发现,一些免疫学因素(如群体反应抗体和延长的冷缺血时间等)和非免疫学因素(移植肾延迟恢复)可增加急性排斥反应和降低移植肾的长期存活。肾移植受者在接受了HLA不同的供肾后,体内产生抗HLA抗体而成为致敏状态。致敏不但与急性排斥有关,而且与慢性排斥及长期存活率也有关。研究显示,在移植大鼠中抗HLA抗体能直接杀死移植后的组织细胞,能够引起超排斥反应、加速性排斥反应、排斥反应和排斥反应,最终导致移植器官功能丧失移植失败。近年来,随着肾脏疾病增多,肾移植数量也随之增多,2次移植也随之逐步增加,曾经有过妊娠史或输血史的病人都可使受者体内出现抗HLA抗体,则会产生较强的抗性,使该受者处于一种致敏状态,不利于肾脏移植配型。临床肾移植术前,多采用患者与供者之间的淋巴毒交叉配型试验,即供者淋巴细胞+受者血清+补体,以检测受者血清内是否存在有针对特定供者的淋巴细胞毒抗体。国外报告,抗供者淋巴细胞抗体阳性受者,移植后80%会发生超排斥反应,所以此项检查很大程度上能够避免移植术后超排斥反应的发生,但这项检查只能检测受者血清内针对供者特异的抗HLA抗体,不能检测针对其他HLA的抗体,因此还有大部分患者发生移植失败。研究表明,在HLA配型良好的情况下,针对多态性主要组织相容性复合体Ⅰ类相关链的MICA抗体,对移植肾排斥反应、功能延迟、移植物切除、长期存活也有重要影响。移植前的淋巴细胞毒交叉配合试验并不能检测出抗MICA抗体。抗MICA抗体产生的途径尚未完全清楚,可能存在“天然”的致敏途径。且抗MICA抗体可能包含IgM和IgG两种免疫球蛋白类型。本文对入组患者进行MICA抗体检测,前瞻性研究PRA、HLA、MICA抗体对肾移植后的影响。
有研究表明,PRA的存在与排斥反应,慢性血管排斥反应和排斥反应发生均有关系,PRA水平与预敏程度关系密切,移植后发生排斥反应机会增高。肾移植受者的预致敏程度对移植物生存有显著的影响,所以移植前检测受者体内的抗HLA抗体水平(测定PRA)能够有效地选择供者,提高移植肾的生存率。高PRA是肾移植排斥反应的免疫性高危因素,是否可以成为肾移植的预警监测是本研究主要创新点,通过对入组患者的PRA数据的统计分析,探讨群体反应性抗体与肾移植术后排斥反应、排斥反应、移植肾功能延迟、移植失败的关系及应用意义。良好的PRA与HLA、MICA抗体筛选技术是肾移植患者长期存活和术后恢复肾功能的有利条件,而PRA值的升高可直接直接造成移植肾的排斥反应、功能延迟、移植失败,检测肾移植患者术前术后PRA,特别是确定高敏感移植受者体内抗体的性质意义重大。本研究通过PRA与HLA、MICA抗体检测了解肾移植受者的免疫排斥基础因素,更好的预防治疗肾移植术后的排斥反应、功能延迟、移植失败等情况。
目的
1、研究PRA与HLA、MICA抗体筛选技术,确定切实可靠筛选项目及技术进行入组患者检测。
2、研究移植肾丢失前组织内HLA与MICA抗体产生情况与PRA水平变化的关系
3、研究PRA与HLA、MICA抗体对排斥反应、移植肾功能延迟、移植失败的预测意义。
4、研究PRA与HLA、MICA抗体检测是否可作为临床治疗效果判定指标。
方法
1、选择入组患者211例进行研究,按照术后6个月内发生的排斥反应、移植肾功能延迟、移植失败,分层随机化法随机分为正常组、排斥反应组、移植肾功能延迟组、移植失败组进行研究。
2、采用ELISA法对外周血PRA进行检测,对比PRA阳性、阴性患者排斥反应、移植肾功能延迟、移植失败发生率。
3、采用流式细胞仪检测肾活检组织PRA、HLA、MICA抗体。
4、采用ELISA法检测外周血HLA、MICA抗体。
5、采用肾活检技术对排斥反应组、移植肾功能延迟组、移植失败组患者进行组织学检测。
6、与其他中心合作,设定共同观察样本,共同完成本研究。
7、观察各组术前PRA、HLA、MICA抗体水平变化并进行比较。
8、观察术后6个月内各组PRA、HLA、MICA抗体水平进行比较。
9、观察排斥反应组、移植肾功能延迟组、移植失败组肾活检组织中PRA、HLA、 MICA抗体水平进行比较。
10、统计学分析：GraphPad Prism统计分析软件5.0对所有数据进行t检验或方差分析并进行多重比较,P<0.05表示具有显著性差异。数值用平均值±标准差或者标准误表示,采用Spearman等级相关的方法,对PRA、HLA、MICA抗体水平进行相关性分析。
结果
1、术前211例患者出现PRA、HLA、MICA抗体例数比较(X2=3.55、3.21、3.22,P>0.05,无显著性差异)。
2、术前PRA阴性与阳性患者6个月内发生排斥、移植肾功能延迟、切除移植肾比较(X2=5.22、5.33、5.65,P<0.05,具有显著性差异)。
3、术前PRA阴性与阳性患者PRA、HLA、MICA抗体之间水平关系比较(t=6.22、7.33、6.65,P<0.05,具有显著性差异)。
4、排斥组、移植肾功能延迟组、切除移植肾比较组PRA、HLA、MICA抗体之间关系比较(t=6.45、6.65、6.89,P<0.05,具有显著性差异)。
5、术前PRA阳性组患者中PRA值在10-30%与PRA≥30%,术后排斥、延迟恢复、切除移植肾比较(X2=5.02、5.13、5.75,P<0.05,具有显著性差异)。
6、术前PRA阳性组患者中PRA值在10-30%与PRA≥30%,PRA、HLA、MICA抗体之间水平关系比较(t=5.65、6.45、6.75,P<0.05,具有显著性差异)。
7、移植后PRA转为阳性者与术后PRA仍为阴性的患者中术后排斥、延迟恢复、切除移植肾比较(X2=4.62、4.73、5.15,P<0.05,具有显著性差异)。
8、移植后PRA转为阳性者与术后PRA仍为阴性的患者PRA、HLA、MICA抗体之间水平关系比较(t=5.43、6.65、6.76,P<0.05,具有显著性差异)。
9、排斥组、移植肾功能延迟组、肾切除组PRA、HLA、MICA抗体与血清肌酐之间关系比较(t=6.21、7.87、8.94、8.21,P<0.05,具有显著性差异)。
10、各组间PRA、HLA、MICA抗体变化呈正相关(rs=0.614,P<0.05)。
结论
1、术前检测PRA、HLA、MICA抗体具有重要临床意义,尤其对有过手术、输血、妊娠史的患者更有意义。
2、PRA、HLA、MICA抗体的检测,可准确地预测和诊断排斥、移植肾功能延迟的发生。
3、PRA检测可作为临床治疗效果判定指标。
4、HLA与ICA抗体术可能是排斥的原因。
5、PRA水平检测可以作为肾移植排斥反应的预警指标。
6、PRA、HLA、MICA抗体水平增高是肾移植术后排斥反应发生和进展的相关因素,参与肾移植术后排斥反应。
7、PRA与HLA、MICA抗体的水平呈正相关,因此PRA高表达患者易发生排斥及功能延缓或失功。
8、推荐采用PRA与HLA、MICA抗体联合检测作为肾移植患者术前筛选。
9、在移植后应密切监测PRA水平的变化,由此可以帮助临床医师准确地预测和诊断急性排斥并在指导治疗中发挥重要的作用,即能够近早地采取抗排斥治疗措施,更大程度上挽救移植肾的功能,提高移植成功率
10、PRA抗体检测对于预测移植物失功,此外,PRA抗体检测结合血清肌酐更有意义。
创新点
1、采用免疫组化ELISA法对外周血PRA、HLA、MICA抗体进行检测。
2、采用肾活检技术进行组织学检测
3、采用流式细胞仪检测肾活检组织PRA、HLA、MICA抗体。
4、采用ELISA法检测外周血及肾活检组织HLA、MICA抗体。
5、探讨术前检测PRA、HLA、MICA抗体临床意义。
6、探讨PRA、HLA、MICA抗体在肾移植术后排斥反应、移植肾功能延迟、移植失败中发生发展机制。
7、探讨肾移植术后排斥反应、移植肾功能延迟、移植失败的发生与发展是一个多因素、多步骤的渐进过程PRA、HLA、MICA抗体相互协同发挥着重要作用,是肾移植术后排斥反应、移植肾功能延迟、移植失败的免疫学基础。
Panel reactive antibody is a IgG type of organism humoral immune antibodies, i.e. panel reactive antibody against HLA-IgG, mainly targeting human HLA antigen, strong specificity. Whether a surgical field tissue transplantation preoperative screening for sensitized recipients are important indicators, and allograft rejection and survival rate is closely related to has become a research hotspot. As a result of human leukocyte antigen diversity, the corresponding antibody is also diverse. HLA donor-recipient matching good rejection and promote the recovery of graft function better, and can reduce the transplant recipients sensitized, can make the long survival after renal transplantation. Research has found, some immunological factors (such as population reactive antibody and prolonged cold ischemia time) and immunological factors (graft delayed recovery) can increase the acute rejection of renal transplantation and reduced long-term survival. Renal transplant recipients in the accepted HLA different donor kidney, produced in vivo anti HLA antibody and become sensitized state. Sensitized not only with acute rejection, and chronic rejection and long-term survival rates are also related to. Research shows that, in a transplanted rat anti HLA antibodies can directly kill after transplantation and the tissue cells, can cause the rejection, accelerated rejection, rejection and graft rejection, leading to eventual graft loss of organ function of graft failure. In recent years, with the increase of the number of kidney disease, kidney transplantation also subsequently grow in quantity,2transplant also gradually increase, had pregnancy history or the history of blood transfusion of the patient can make the recipients in anti HLA antibody, can produce a strong resistance, so that the recipients in a sensitized state, not for kidney transplantation. Clinical before renal transplantation, the patients with donor between lymphoid cytotoxic cross-match, whereby the donor lymphocyte+recipients with serum+complement, in order to detect the recipients with serum whether there are specific to a particular donor lymphocyte antibody. Foreign reports, of donor lymphocyte antibody positive recipients, graft after80%will occur over rejection, so this examination can largely avoid transplantation after ultra rejection, but it can only be detected in the serum of the recipients of donor specific antibody against the HLA, could not be detected in other HLA antibody, so most patients with graft failure. Research shows that, in the HLA matching condition, the polymorphic major histocompatibility complex class I chain-related MICA antibody, on renal allograft rejection, delayed graft function, excision, long-term survival also has an important influence on. Pretransplant lymphocyte cytotoxicity crossmatch test does not detect the anti MICA antibody. Anti MICA antibody pathway is not yet fully understood, there may be a" natural" sensitized ways. And anti MICA antibody may include IgM and IgG two immunoglobulin type. This article on the group of patients with MICA antibody detection, prospective study of PRA, HLA, MICA antibodies after kidney transplantation effect. Studies have shown that, in the presence of PRA and rejection, chronic vascular rejection and graft rejection are relations, PRA levels and the susceptibility of closely related, transplantation rejection after the opportunity to increase. Renal transplant recipients pre degree of sensitization on graft survival has a significant effect, so before transplantation recipients in vivo detection of anti HLA antibody levels (of PRA) can effectively select donor, improve renal graft survival rate. High PRA is the rejection of kidney transplantation immunological risk factors, whether can become renal transplant monitoring is the main innovation, through into the group of patients with PRA data statistical analysis, discussion of panel reactive antibody and renal transplantation rejection, rejection, delayed graft function, graft failure relationship and application. Good PRA and HLA, MICA antibody screening technology is long-term survival in renal transplant patients and postoperative recovery of renal function in favorable conditions, and the increase of the PRA value can be directly cause renal transplant rejection, delayed function, graft failure, detection, of renal transplantation patients before and after operation in PRA, especially in determining high sensitive transplantation recipients of in vivo antibody nature of great significance. The study by PRA and HLA, MICA antibody detection in understanding the immune rejection in renal transplant recipients based factors, better preventive therapy after renal transplantation rejection, delayed function, graft failure etc.
Objective
1、PRA and HLA, MICA antibody screening technique, determine the reliable screening project and technology into the group of patients detection.
2、study of renal graft loss before the organization of HLA and MICA antibody and PRA relation
3、PRA and HLA, MICA antibodies on rejection, delayed graft function, predictive of graft failure.
4、PRA and HLA, MICA antibody detection can be used as a clinical therapeutic effect index.
Method
1、choose to join the group in211cases study, according to operation6months after the onset of rejection, delayed graft function, graft failure, stratified randomization were randomly divided into normal group, rejection, delayed graft function, graft failure group by group.
2、using the method of ELISA on peripheral blood PRA were detected, compared to PRA positive, negative patients with rejection, delayed graft function, incidence of graft failure.
3,using flow cytometry for the detection of renal biopsy tissue PRA, HLA, MICA antibody.
4, using the ELISA method for the detection of peripheral blood HLA, MICA antibody.
5、the renal biopsy technique for rejection, delayed graft function group, graft failure patients for histological detection.
6、and the other center, set the common observation of samples, together to complete this study.
7、observed the preoperative PRA, HLA, MICA and compare the changes of antibody level in.
8、observed6months after the operation in each group of PRA, HLA, MICA antibody levels were compared.
9、observation group, rejection, delayed graft function group, graft failure group renal biopsy tissue PRA, HLA, MICA antibody levels were compared.
10、the statistical analysis:GraphPad Prism statistical analysis software in5for all data were analyzed by t test or analysis of variance and multiple comparisons, says P<0.05has significant difference. Numerical mean±standard deviation or standard error representation, by using Spearman rank correlation methods, PRA, HLA, MICA antibody levels were correlation analysis.
Result
1、before the operation and211cases PRA, HLA, MICA antibodies were compared (X2=3.55,3.21,3.22, P>0.05, no significant difference).
2、preoperative PRA negative and positive patients within6months of the onset of rejection, delayed graft function after renal transplantation, resection of comparison (X2=5.22,5.33,5.65, P<0.05, with significant difference).
3、preoperative PRA patients with negative and positive PRA, HLA, MICA antibody level relationship between (t=6.22,7.33,6.65, P<0.05, with significant difference).
4、group, rejection, delayed graft function after renal transplantation compared with resection group, group PRA, HLA, MICA relationship between antibodies to compare (t=6.45,6.65,6.89, P<0.05, with significant difference).
5、preoperative PRA positive patients with PRA in10-30%and PRA≥30%, postoperative rejection, delayed recovery of renal transplantation, resection of comparison (X2=5.02,5.13,5.75, P<0.05, with significant difference).
6、preoperative PRA positive patients with PRA in10-30%and PRA≥30%, PRA, HLA, MICA antibody level relationship between (t=5.65,6.45,6.75, P<0.05, with significant difference).
7、PRA after transplantation into the positive and the postoperative PRA remained seronegative patients postoperative rejection, delayed recovery of renal transplantation, resection of comparison (X2=4.62,4.73,5.15, P<0.05, with significant difference).
8、PRA after transplantation into the positive and the postoperative PRA was negative patients with PRA, HLA, MICA antibody level relationship between (t=5.43,6.65,6.76, P<0.05, with significant difference).
9、group, rejection, delayed graft function group, the nephrectomy group PRA, HLA, MICA antibodies and serum creatinine (t=6.21,7.87between relations,8.94,8.21, P<0.05, with significant difference).
10、groups PRA, HLA, MICA antibody changes were positively correlated (rs=0.614, P<0.05).
Conclusion
1、preoperative detection of PRA, HLA, MICA antibodies is of great clinical significance, especially to have operation, blood transfusion, pregnancy in patients with a history of more.
2、PRA, HLA, MICA antibody detection, can be accurately predicted and a diagnosis of exclusion, delayed graft function occurred.
3、PRA detection can be used as a clinical therapeutic effect index.
4、HLA and MICA antibodies excision may be a reason for exclusion.
5、PRA levels can be used as a renal allograft rejection in the early warning index.
6、PRA, HLA, MICA antibody levels after renal transplantation is rejection and progression of the related factors, involved in rejection after renal transplantation.
7、PRA and HLA, MICA antibody levels were positively correlated, so the high expression of PRA patients are prone to rejection and the function of delay or failure.
8、recommend the use of PRA and HLA, MICA antibody detection as a renal transplant patients for preoperative screening.
9、after transplantation should be monitored closely the change of PRA level, which can help clinicians to accurately forecast and diagnosis of acute rejection and in guiding therapy play an important role, i.e. to close early to take anti-rejection treatment measures, to a greater extent save the renal allograft function, improve the success rate of transplantation.
10、PRA antibody test for predicting graft failure, in addition, PRA antibody detection in combination with serum creatinine more meaningful.
Innovation point
1、by using immunohistochemistry ELISA method of peripheral blood PRA, HLA, MICA antibody detection.
2、the renal biopsy for histological detection
3、using flow cytometry for the detection of renal biopsy tissue PRA, HLA, MICA antibody.
4、using the method of ELISA detection in peripheral blood and renal tissues of HLA, MICA antibody.
5、explore preoperative detection of PRA, HLA, MICA antibodies and clinical significance.
6、PRA, HLA, MICA antibody in the rejection after renal transplantation, delayed graft function, graft failure occurred in development mechanism.
7、rejection after renal transplantation, delayed graft function, graft failure occurred and development is a multiple factor, multiple steps of the gradual process of PRA, HLA, MICA antibody synergistic interaction plays an important role, is the rejection after renal transplantation, delayed graft function, graft failure:immunology.
有研究表明,PRA的存在与排斥反应,慢性血管排斥反应和排斥反应发生均有关系,PRA水平与预敏程度关系密切,移植后发生排斥反应机会增高。肾移植受者的预致敏程度对移植物生存有显著的影响,所以移植前检测受者体内的抗HLA抗体水平(测定PRA)能够有效地选择供者,提高移植肾的生存率。高PRA是肾移植排斥反应的免疫性高危因素,是否可以成为肾移植的预警监测是本研究主要创新点,通过对入组患者的PRA数据的统计分析,探讨群体反应性抗体与肾移植术后排斥反应、排斥反应、移植肾功能延迟、移植失败的关系及应用意义。良好的PRA与HLA、MICA抗体筛选技术是肾移植患者长期存活和术后恢复肾功能的有利条件,而PRA值的升高可直接直接造成移植肾的排斥反应、功能延迟、移植失败,检测肾移植患者术前术后PRA,特别是确定高敏感移植受者体内抗体的性质意义重大。本研究通过PRA与HLA、MICA抗体检测了解肾移植受者的免疫排斥基础因素,更好的预防治疗肾移植术后的排斥反应、功能延迟、移植失败等情况。
目的
1、研究PRA与HLA、MICA抗体筛选技术,确定切实可靠筛选项目及技术进行入组患者检测。
2、研究移植肾丢失前组织内HLA与MICA抗体产生情况与PRA水平变化的关系
3、研究PRA与HLA、MICA抗体对排斥反应、移植肾功能延迟、移植失败的预测意义。
4、研究PRA与HLA、MICA抗体检测是否可作为临床治疗效果判定指标。
方法
1、选择入组患者211例进行研究,按照术后6个月内发生的排斥反应、移植肾功能延迟、移植失败,分层随机化法随机分为正常组、排斥反应组、移植肾功能延迟组、移植失败组进行研究。
2、采用ELISA法对外周血PRA进行检测,对比PRA阳性、阴性患者排斥反应、移植肾功能延迟、移植失败发生率。
3、采用流式细胞仪检测肾活检组织PRA、HLA、MICA抗体。
4、采用ELISA法检测外周血HLA、MICA抗体。
5、采用肾活检技术对排斥反应组、移植肾功能延迟组、移植失败组患者进行组织学检测。
6、与其他中心合作,设定共同观察样本,共同完成本研究。
7、观察各组术前PRA、HLA、MICA抗体水平变化并进行比较。
8、观察术后6个月内各组PRA、HLA、MICA抗体水平进行比较。
9、观察排斥反应组、移植肾功能延迟组、移植失败组肾活检组织中PRA、HLA、 MICA抗体水平进行比较。
10、统计学分析：GraphPad Prism统计分析软件5.0对所有数据进行t检验或方差分析并进行多重比较,P<0.05表示具有显著性差异。数值用平均值±标准差或者标准误表示,采用Spearman等级相关的方法,对PRA、HLA、MICA抗体水平进行相关性分析。
结果
1、术前211例患者出现PRA、HLA、MICA抗体例数比较(X2=3.55、3.21、3.22,P>0.05,无显著性差异)。
2、术前PRA阴性与阳性患者6个月内发生排斥、移植肾功能延迟、切除移植肾比较(X2=5.22、5.33、5.65,P<0.05,具有显著性差异)。
3、术前PRA阴性与阳性患者PRA、HLA、MICA抗体之间水平关系比较(t=6.22、7.33、6.65,P<0.05,具有显著性差异)。
4、排斥组、移植肾功能延迟组、切除移植肾比较组PRA、HLA、MICA抗体之间关系比较(t=6.45、6.65、6.89,P<0.05,具有显著性差异)。
5、术前PRA阳性组患者中PRA值在10-30%与PRA≥30%,术后排斥、延迟恢复、切除移植肾比较(X2=5.02、5.13、5.75,P<0.05,具有显著性差异)。
6、术前PRA阳性组患者中PRA值在10-30%与PRA≥30%,PRA、HLA、MICA抗体之间水平关系比较(t=5.65、6.45、6.75,P<0.05,具有显著性差异)。
7、移植后PRA转为阳性者与术后PRA仍为阴性的患者中术后排斥、延迟恢复、切除移植肾比较(X2=4.62、4.73、5.15,P<0.05,具有显著性差异)。
8、移植后PRA转为阳性者与术后PRA仍为阴性的患者PRA、HLA、MICA抗体之间水平关系比较(t=5.43、6.65、6.76,P<0.05,具有显著性差异)。
9、排斥组、移植肾功能延迟组、肾切除组PRA、HLA、MICA抗体与血清肌酐之间关系比较(t=6.21、7.87、8.94、8.21,P<0.05,具有显著性差异)。
10、各组间PRA、HLA、MICA抗体变化呈正相关(rs=0.614,P<0.05)。
结论
1、术前检测PRA、HLA、MICA抗体具有重要临床意义,尤其对有过手术、输血、妊娠史的患者更有意义。
2、PRA、HLA、MICA抗体的检测,可准确地预测和诊断排斥、移植肾功能延迟的发生。
3、PRA检测可作为临床治疗效果判定指标。
4、HLA与ICA抗体术可能是排斥的原因。
5、PRA水平检测可以作为肾移植排斥反应的预警指标。
6、PRA、HLA、MICA抗体水平增高是肾移植术后排斥反应发生和进展的相关因素,参与肾移植术后排斥反应。
7、PRA与HLA、MICA抗体的水平呈正相关,因此PRA高表达患者易发生排斥及功能延缓或失功。
8、推荐采用PRA与HLA、MICA抗体联合检测作为肾移植患者术前筛选。
9、在移植后应密切监测PRA水平的变化,由此可以帮助临床医师准确地预测和诊断急性排斥并在指导治疗中发挥重要的作用,即能够近早地采取抗排斥治疗措施,更大程度上挽救移植肾的功能,提高移植成功率
10、PRA抗体检测对于预测移植物失功,此外,PRA抗体检测结合血清肌酐更有意义。
创新点
1、采用免疫组化ELISA法对外周血PRA、HLA、MICA抗体进行检测。
2、采用肾活检技术进行组织学检测
3、采用流式细胞仪检测肾活检组织PRA、HLA、MICA抗体。
4、采用ELISA法检测外周血及肾活检组织HLA、MICA抗体。
5、探讨术前检测PRA、HLA、MICA抗体临床意义。
6、探讨PRA、HLA、MICA抗体在肾移植术后排斥反应、移植肾功能延迟、移植失败中发生发展机制。
7、探讨肾移植术后排斥反应、移植肾功能延迟、移植失败的发生与发展是一个多因素、多步骤的渐进过程PRA、HLA、MICA抗体相互协同发挥着重要作用,是肾移植术后排斥反应、移植肾功能延迟、移植失败的免疫学基础。
Panel reactive antibody is a IgG type of organism humoral immune antibodies, i.e. panel reactive antibody against HLA-IgG, mainly targeting human HLA antigen, strong specificity. Whether a surgical field tissue transplantation preoperative screening for sensitized recipients are important indicators, and allograft rejection and survival rate is closely related to has become a research hotspot. As a result of human leukocyte antigen diversity, the corresponding antibody is also diverse. HLA donor-recipient matching good rejection and promote the recovery of graft function better, and can reduce the transplant recipients sensitized, can make the long survival after renal transplantation. Research has found, some immunological factors (such as population reactive antibody and prolonged cold ischemia time) and immunological factors (graft delayed recovery) can increase the acute rejection of renal transplantation and reduced long-term survival. Renal transplant recipients in the accepted HLA different donor kidney, produced in vivo anti HLA antibody and become sensitized state. Sensitized not only with acute rejection, and chronic rejection and long-term survival rates are also related to. Research shows that, in a transplanted rat anti HLA antibodies can directly kill after transplantation and the tissue cells, can cause the rejection, accelerated rejection, rejection and graft rejection, leading to eventual graft loss of organ function of graft failure. In recent years, with the increase of the number of kidney disease, kidney transplantation also subsequently grow in quantity,2transplant also gradually increase, had pregnancy history or the history of blood transfusion of the patient can make the recipients in anti HLA antibody, can produce a strong resistance, so that the recipients in a sensitized state, not for kidney transplantation. Clinical before renal transplantation, the patients with donor between lymphoid cytotoxic cross-match, whereby the donor lymphocyte+recipients with serum+complement, in order to detect the recipients with serum whether there are specific to a particular donor lymphocyte antibody. Foreign reports, of donor lymphocyte antibody positive recipients, graft after80%will occur over rejection, so this examination can largely avoid transplantation after ultra rejection, but it can only be detected in the serum of the recipients of donor specific antibody against the HLA, could not be detected in other HLA antibody, so most patients with graft failure. Research shows that, in the HLA matching condition, the polymorphic major histocompatibility complex class I chain-related MICA antibody, on renal allograft rejection, delayed graft function, excision, long-term survival also has an important influence on. Pretransplant lymphocyte cytotoxicity crossmatch test does not detect the anti MICA antibody. Anti MICA antibody pathway is not yet fully understood, there may be a" natural" sensitized ways. And anti MICA antibody may include IgM and IgG two immunoglobulin type. This article on the group of patients with MICA antibody detection, prospective study of PRA, HLA, MICA antibodies after kidney transplantation effect. Studies have shown that, in the presence of PRA and rejection, chronic vascular rejection and graft rejection are relations, PRA levels and the susceptibility of closely related, transplantation rejection after the opportunity to increase. Renal transplant recipients pre degree of sensitization on graft survival has a significant effect, so before transplantation recipients in vivo detection of anti HLA antibody levels (of PRA) can effectively select donor, improve renal graft survival rate. High PRA is the rejection of kidney transplantation immunological risk factors, whether can become renal transplant monitoring is the main innovation, through into the group of patients with PRA data statistical analysis, discussion of panel reactive antibody and renal transplantation rejection, rejection, delayed graft function, graft failure relationship and application. Good PRA and HLA, MICA antibody screening technology is long-term survival in renal transplant patients and postoperative recovery of renal function in favorable conditions, and the increase of the PRA value can be directly cause renal transplant rejection, delayed function, graft failure, detection, of renal transplantation patients before and after operation in PRA, especially in determining high sensitive transplantation recipients of in vivo antibody nature of great significance. The study by PRA and HLA, MICA antibody detection in understanding the immune rejection in renal transplant recipients based factors, better preventive therapy after renal transplantation rejection, delayed function, graft failure etc.
Objective
1、PRA and HLA, MICA antibody screening technique, determine the reliable screening project and technology into the group of patients detection.
2、study of renal graft loss before the organization of HLA and MICA antibody and PRA relation
3、PRA and HLA, MICA antibodies on rejection, delayed graft function, predictive of graft failure.
4、PRA and HLA, MICA antibody detection can be used as a clinical therapeutic effect index.
Method
1、choose to join the group in211cases study, according to operation6months after the onset of rejection, delayed graft function, graft failure, stratified randomization were randomly divided into normal group, rejection, delayed graft function, graft failure group by group.
2、using the method of ELISA on peripheral blood PRA were detected, compared to PRA positive, negative patients with rejection, delayed graft function, incidence of graft failure.
3,using flow cytometry for the detection of renal biopsy tissue PRA, HLA, MICA antibody.
4, using the ELISA method for the detection of peripheral blood HLA, MICA antibody.
5、the renal biopsy technique for rejection, delayed graft function group, graft failure patients for histological detection.
6、and the other center, set the common observation of samples, together to complete this study.
7、observed the preoperative PRA, HLA, MICA and compare the changes of antibody level in.
8、observed6months after the operation in each group of PRA, HLA, MICA antibody levels were compared.
9、observation group, rejection, delayed graft function group, graft failure group renal biopsy tissue PRA, HLA, MICA antibody levels were compared.
10、the statistical analysis:GraphPad Prism statistical analysis software in5for all data were analyzed by t test or analysis of variance and multiple comparisons, says P<0.05has significant difference. Numerical mean±standard deviation or standard error representation, by using Spearman rank correlation methods, PRA, HLA, MICA antibody levels were correlation analysis.
Result
1、before the operation and211cases PRA, HLA, MICA antibodies were compared (X2=3.55,3.21,3.22, P>0.05, no significant difference).
2、preoperative PRA negative and positive patients within6months of the onset of rejection, delayed graft function after renal transplantation, resection of comparison (X2=5.22,5.33,5.65, P<0.05, with significant difference).
3、preoperative PRA patients with negative and positive PRA, HLA, MICA antibody level relationship between (t=6.22,7.33,6.65, P<0.05, with significant difference).
4、group, rejection, delayed graft function after renal transplantation compared with resection group, group PRA, HLA, MICA relationship between antibodies to compare (t=6.45,6.65,6.89, P<0.05, with significant difference).
5、preoperative PRA positive patients with PRA in10-30%and PRA≥30%, postoperative rejection, delayed recovery of renal transplantation, resection of comparison (X2=5.02,5.13,5.75, P<0.05, with significant difference).
6、preoperative PRA positive patients with PRA in10-30%and PRA≥30%, PRA, HLA, MICA antibody level relationship between (t=5.65,6.45,6.75, P<0.05, with significant difference).
7、PRA after transplantation into the positive and the postoperative PRA remained seronegative patients postoperative rejection, delayed recovery of renal transplantation, resection of comparison (X2=4.62,4.73,5.15, P<0.05, with significant difference).
8、PRA after transplantation into the positive and the postoperative PRA was negative patients with PRA, HLA, MICA antibody level relationship between (t=5.43,6.65,6.76, P<0.05, with significant difference).
9、group, rejection, delayed graft function group, the nephrectomy group PRA, HLA, MICA antibodies and serum creatinine (t=6.21,7.87between relations,8.94,8.21, P<0.05, with significant difference).
10、groups PRA, HLA, MICA antibody changes were positively correlated (rs=0.614, P<0.05).
Conclusion
1、preoperative detection of PRA, HLA, MICA antibodies is of great clinical significance, especially to have operation, blood transfusion, pregnancy in patients with a history of more.
2、PRA, HLA, MICA antibody detection, can be accurately predicted and a diagnosis of exclusion, delayed graft function occurred.
3、PRA detection can be used as a clinical therapeutic effect index.
4、HLA and MICA antibodies excision may be a reason for exclusion.
5、PRA levels can be used as a renal allograft rejection in the early warning index.
6、PRA, HLA, MICA antibody levels after renal transplantation is rejection and progression of the related factors, involved in rejection after renal transplantation.
7、PRA and HLA, MICA antibody levels were positively correlated, so the high expression of PRA patients are prone to rejection and the function of delay or failure.
8、recommend the use of PRA and HLA, MICA antibody detection as a renal transplant patients for preoperative screening.
9、after transplantation should be monitored closely the change of PRA level, which can help clinicians to accurately forecast and diagnosis of acute rejection and in guiding therapy play an important role, i.e. to close early to take anti-rejection treatment measures, to a greater extent save the renal allograft function, improve the success rate of transplantation.
10、PRA antibody test for predicting graft failure, in addition, PRA antibody detection in combination with serum creatinine more meaningful.
Innovation point
1、by using immunohistochemistry ELISA method of peripheral blood PRA, HLA, MICA antibody detection.
2、the renal biopsy for histological detection
3、using flow cytometry for the detection of renal biopsy tissue PRA, HLA, MICA antibody.
4、using the method of ELISA detection in peripheral blood and renal tissues of HLA, MICA antibody.
5、explore preoperative detection of PRA, HLA, MICA antibodies and clinical significance.
6、PRA, HLA, MICA antibody in the rejection after renal transplantation, delayed graft function, graft failure occurred in development mechanism.
7、rejection after renal transplantation, delayed graft function, graft failure occurred and development is a multiple factor, multiple steps of the gradual process of PRA, HLA, MICA antibody synergistic interaction plays an important role, is the rejection after renal transplantation, delayed graft function, graft failure:immunology.
引文
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