炎症反应在幼年特发性关节炎的作用研究
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摘要
第一部分
幼年特发性关节炎189例临床分析
目的
探讨幼年特发性关节炎(JIA)的临床表现、分类及实验室检查特点,以及炎症指标在临床评价中的作用。
方法
总结2003年1月～2013年6月我院住院收治的189例JIA患儿临床症状、体征、及实验室检查资料,以2001年国际风湿病学联盟儿科专家组制订的JIA标准进行分类,并对JIA患儿的临床表现、实验室检查进行回顾性分析。
结果
1、本组JIA患儿男100例,女89例。其中全身型119例(62.9%),少关节型13例(6.9%),多关节型(RF阳性)16例(8.5%),多关节型(RF阴性)15例(7.9%),与附着点炎性反应相关的关节炎13例(6.9%),银屑病性关节炎3例(1.6%),未分类的关节炎10例(5.3%)。
2、全身型临床表现为发热、皮疹、淋巴结大、肝大和(或)脾大等非特异性症征,病程1年以上者未再发现肿瘤及其他疾病。
3、全身型患者炎症指标升高更明显,包括血WBC升高、ESR增快以及Hb和血清白蛋白的降低。
4、关节型患儿可见类风湿因子(RF)、抗核抗体(ANA)、人类白细胞抗原(HLA)—B27和抗环瓜氨酸肽抗体(anti-CCP)等抗体不同程度的阳性。
5、血清白蛋白作为负性炎症指标与血WBC、ESR和Hb明显相关。
结论
1、本组JIA病例中以全身型为最多见,对缺少关节炎表现的患儿应观察至少1年以上、排除其他疾病后才能确诊JIA全身型；
2、全身型JIA患者的炎症指标较关节型更明显,血清白蛋白可与血WBC、ESR和Hb一起作为负性炎症指标用于临床评估。
第二、三部分
炎症反应在幼年特发性关节炎全身型的作用研究
目的
检测SJIA患儿血清TNF-α、IL-1β、IL-6及IL-18等炎症因子水平,了解NLRP3基因多态性在SJIA患儿中的分布情况,探讨NLRP3基因多态性与SJIA的关系。
方法
收集我院确诊并长期我院随诊的26例活动期SJIA患儿全血及血清。外周血清测定TNF-α、IL-1β、IL-6及IL-18水平,分析其在SJIA患儿中的表达情况。全血提取DNA, PCR法扩增NLRP3基因,测定NLRP3基因9个外显子序列,分析各多态性位点基因型频率、等位基因分布与SJIA发病的关系。39名健康儿童作为对照组留取血清测定细胞因子。
结果
1、SJIA患儿血清中TNF-α、IL-1β水平与对照组相比无差别。
2、有关节症状和无关节症状的患儿相比TNF-α、IL-1β水平无差异,而IL-6、IL-18水平均高于对照组,两组间无差异。
3、SJIA患儿血清IL-6水平与ESR呈正相关,IL-18水平与WBC、ESR呈正相关。
4、在SJIA患儿NLRP3基因中发现3个SNP, rs35829419C>A, rs7525979C>T, rs3806268G>A。
5、3个SNP位点的基因频率、基因型与人群分布无差异。
结论
1、外周血IL-6及IL-18水平与ESR、WBC等炎症指标相关,能够提示疾病的活动状态。
2、NLRP3基因是否为SJIA发病的易感基因仍需进一步探讨。
First Part
The Clinical Features Of189Cases With Juvenile Idiopathic Arthritis
Objective
To investigate the characteristics of clinical manifestation, classification, laboratory tests and the effect of inflammatory indices in clinical assessment of juvenile idiopathic arthritis (JIA).
Methods
Reviewing their clinical features according to the International League of Association for Rheumatology (ILAR) classification criteria, collected data of189children with JIA. A clinical retrospective analysis was carried out.
Results
1、Of189cases, including100male and89female,119cases with systemic JIA (62.9%),13cases with oligoarthritis (6.9%),16cases with polyarthritis RF positive (8.5%),15cases with polyarthritis RF negative (7.9%),3cases with psoriatic arthritis (1.6%),13cases with enthesitis-related JIA (6.9%) and10cases with undefined JIA (5.3%).
2、Systemic JIA (SJIA) was non-specific in terms of clinical manifestations, including fever, rash, lymphadenopathy, hepatomegaly and (or) splenomegaly et al, the clinical course was more than one year and excluded tumor and other diseases.
3、Systemic JIA laboratory tests showed a marked inflammatory response with leucytosis, very high CRP and ESR, a decrease in hemoglobin and serum albumin concentrations.
4、There were different positive rate for RF, ANA, HLA-B27and anti-CCP in the other subsets.
5、Serum albumin as a negative acute-phase protein was correlated inversely with WBC count and ESR, correlated positively with hemoglobin.
Conclusions
1、Patients with systemic JIA were most common; some cases absent arthritis should be diagnosed after more than one year, and excluded other diseases.
2、Laboratory test showed a marked inflammatory response in SJIA, serum albumin as a negative acute-phase protein and WBC count, ESR, hemoglobin should be used in clinical assessment of SJIA.
Second and third Part
The role of inflammation in systemic juvenile idiopathic arthritis Abstract
Object:
To detected the serum levels of TNF-α IL-1β、IL-6and IL-18.T0investigate whether single nucleotide polymorphisms (SNPs) within the gene NLRP3, which are known to contribute to the risk of autoinflammortary diseases, confer an increased risk of susceptibility to systemic JIA.
Method:
26cases with SJIA and39healthy individuals were enrolled. All the9exons were directly sequenced to identify and characterize the single nucleotide polymorphisms in SJIA. The genotypic and allelic frequencies of SNPS were analyzed with case-control study, both cases and controls were detected the serum levels of TNF-α、IL-1β、IL-6and IL-18.
Results:
1. The serum concentrations of TNF-a and IL-1β were no different in patients and controls.
2. The serum concentrations of IL-6and IL-18were significantly higher in patients than that in controls. The patients were divided into two groups, one with arthritis, and the other with non-arthritis. The serum concentrations of IL-6and IL-18were no different in the two groups.
3. Serum concentration of IL-6was positively correlated with ESR and IL-18was positively correlated with ESR and WBC.
4. Three SNPS in exon3of NLRP3were identified, rs35829419C>A, rs7525979C> T, rs3806268G>A.
5. The allele frequency was no significant differences in SJIA patients and controls (p>0.05).
Conclusion
1. The serum levels of IL-6and IL-18were correlated positively with WBC and ESR, maybe presented the activity of S JIA.
2. More research were need to carry out to confirm the NLRP3associated with the susceptibility of S JIA.
幼年特发性关节炎189例临床分析
目的
探讨幼年特发性关节炎(JIA)的临床表现、分类及实验室检查特点,以及炎症指标在临床评价中的作用。
方法
总结2003年1月～2013年6月我院住院收治的189例JIA患儿临床症状、体征、及实验室检查资料,以2001年国际风湿病学联盟儿科专家组制订的JIA标准进行分类,并对JIA患儿的临床表现、实验室检查进行回顾性分析。
结果
1、本组JIA患儿男100例,女89例。其中全身型119例(62.9%),少关节型13例(6.9%),多关节型(RF阳性)16例(8.5%),多关节型(RF阴性)15例(7.9%),与附着点炎性反应相关的关节炎13例(6.9%),银屑病性关节炎3例(1.6%),未分类的关节炎10例(5.3%)。
2、全身型临床表现为发热、皮疹、淋巴结大、肝大和(或)脾大等非特异性症征,病程1年以上者未再发现肿瘤及其他疾病。
3、全身型患者炎症指标升高更明显,包括血WBC升高、ESR增快以及Hb和血清白蛋白的降低。
4、关节型患儿可见类风湿因子(RF)、抗核抗体(ANA)、人类白细胞抗原(HLA)—B27和抗环瓜氨酸肽抗体(anti-CCP)等抗体不同程度的阳性。
5、血清白蛋白作为负性炎症指标与血WBC、ESR和Hb明显相关。
结论
1、本组JIA病例中以全身型为最多见,对缺少关节炎表现的患儿应观察至少1年以上、排除其他疾病后才能确诊JIA全身型；
2、全身型JIA患者的炎症指标较关节型更明显,血清白蛋白可与血WBC、ESR和Hb一起作为负性炎症指标用于临床评估。
第二、三部分
炎症反应在幼年特发性关节炎全身型的作用研究
目的
检测SJIA患儿血清TNF-α、IL-1β、IL-6及IL-18等炎症因子水平,了解NLRP3基因多态性在SJIA患儿中的分布情况,探讨NLRP3基因多态性与SJIA的关系。
方法
收集我院确诊并长期我院随诊的26例活动期SJIA患儿全血及血清。外周血清测定TNF-α、IL-1β、IL-6及IL-18水平,分析其在SJIA患儿中的表达情况。全血提取DNA, PCR法扩增NLRP3基因,测定NLRP3基因9个外显子序列,分析各多态性位点基因型频率、等位基因分布与SJIA发病的关系。39名健康儿童作为对照组留取血清测定细胞因子。
结果
1、SJIA患儿血清中TNF-α、IL-1β水平与对照组相比无差别。
2、有关节症状和无关节症状的患儿相比TNF-α、IL-1β水平无差异,而IL-6、IL-18水平均高于对照组,两组间无差异。
3、SJIA患儿血清IL-6水平与ESR呈正相关,IL-18水平与WBC、ESR呈正相关。
4、在SJIA患儿NLRP3基因中发现3个SNP, rs35829419C>A, rs7525979C>T, rs3806268G>A。
5、3个SNP位点的基因频率、基因型与人群分布无差异。
结论
1、外周血IL-6及IL-18水平与ESR、WBC等炎症指标相关,能够提示疾病的活动状态。
2、NLRP3基因是否为SJIA发病的易感基因仍需进一步探讨。
First Part
The Clinical Features Of189Cases With Juvenile Idiopathic Arthritis
Objective
To investigate the characteristics of clinical manifestation, classification, laboratory tests and the effect of inflammatory indices in clinical assessment of juvenile idiopathic arthritis (JIA).
Methods
Reviewing their clinical features according to the International League of Association for Rheumatology (ILAR) classification criteria, collected data of189children with JIA. A clinical retrospective analysis was carried out.
Results
1、Of189cases, including100male and89female,119cases with systemic JIA (62.9%),13cases with oligoarthritis (6.9%),16cases with polyarthritis RF positive (8.5%),15cases with polyarthritis RF negative (7.9%),3cases with psoriatic arthritis (1.6%),13cases with enthesitis-related JIA (6.9%) and10cases with undefined JIA (5.3%).
2、Systemic JIA (SJIA) was non-specific in terms of clinical manifestations, including fever, rash, lymphadenopathy, hepatomegaly and (or) splenomegaly et al, the clinical course was more than one year and excluded tumor and other diseases.
3、Systemic JIA laboratory tests showed a marked inflammatory response with leucytosis, very high CRP and ESR, a decrease in hemoglobin and serum albumin concentrations.
4、There were different positive rate for RF, ANA, HLA-B27and anti-CCP in the other subsets.
5、Serum albumin as a negative acute-phase protein was correlated inversely with WBC count and ESR, correlated positively with hemoglobin.
Conclusions
1、Patients with systemic JIA were most common; some cases absent arthritis should be diagnosed after more than one year, and excluded other diseases.
2、Laboratory test showed a marked inflammatory response in SJIA, serum albumin as a negative acute-phase protein and WBC count, ESR, hemoglobin should be used in clinical assessment of SJIA.
Second and third Part
The role of inflammation in systemic juvenile idiopathic arthritis Abstract
Object:
To detected the serum levels of TNF-α IL-1β、IL-6and IL-18.T0investigate whether single nucleotide polymorphisms (SNPs) within the gene NLRP3, which are known to contribute to the risk of autoinflammortary diseases, confer an increased risk of susceptibility to systemic JIA.
Method:
26cases with SJIA and39healthy individuals were enrolled. All the9exons were directly sequenced to identify and characterize the single nucleotide polymorphisms in SJIA. The genotypic and allelic frequencies of SNPS were analyzed with case-control study, both cases and controls were detected the serum levels of TNF-α、IL-1β、IL-6and IL-18.
Results:
1. The serum concentrations of TNF-a and IL-1β were no different in patients and controls.
2. The serum concentrations of IL-6and IL-18were significantly higher in patients than that in controls. The patients were divided into two groups, one with arthritis, and the other with non-arthritis. The serum concentrations of IL-6and IL-18were no different in the two groups.
3. Serum concentration of IL-6was positively correlated with ESR and IL-18was positively correlated with ESR and WBC.
4. Three SNPS in exon3of NLRP3were identified, rs35829419C>A, rs7525979C> T, rs3806268G>A.
5. The allele frequency was no significant differences in SJIA patients and controls (p>0.05).
Conclusion
1. The serum levels of IL-6and IL-18were correlated positively with WBC and ESR, maybe presented the activity of S JIA.
2. More research were need to carry out to confirm the NLRP3associated with the susceptibility of S JIA.
引文
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