炎症反应在幼年特发性关节炎的作用研究

发布时间：2018-06-05 13:41

本文选题：幼年特发性关节炎 + 关节炎　；参考：《北京协和医学院》2014年博士论文

【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, rs35829419CA, rs7525979CT, rs3806268GA。 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。
[Abstract]:Part I Clinical analysis of 189 cases of juvenile idiopathic arthritis Purpose To investigate the clinical manifestations, classification and laboratory features of juvenile idiopathic arthritis (JIA) and the role of inflammatory markers in clinical evaluation. Method The clinical symptoms, signs and laboratory data of 189 cases of JIA hospitalized in our hospital from January 2003 to June 2013 were summarized. The clinical manifestations of children with JIA were classified according to the JIA standard formulated by the Pediatrics expert Group of the International Union of Rheumatology in 2001. The laboratory examination was analyzed retrospectively. Result 1. There were 100 males and 89 females with JIA. There were 119 cases of systemic type, 13 cases of hypoarticular type, 16 cases of polyarticular type RF positive, 15 cases of polyarticular type, 13 cases of psoriatic arthritis, 3 cases of psoriatic arthritis, 10 cases of unclassified arthritis, and 5 cases of unclassified arthritis, among them, 119 cases of systemic type, 13 cases of hypoarticular type, 13 cases of septic arthritis, 3 cases of psoriatic arthritis, and 10 cases of unclassified arthritis, respectively, were found to be 8. 5%, 15 cases were negative for RF and 7. 9%, 13 cases were associated with inflammatory reaction of attachment point, 3 cases were psoriatic arthritis. 2, the clinical manifestations of systemic type were fever, rash, large lymph node, hepatomegaly and / or splenomegaly, and no tumor or other diseases were found in the patients with disease course of more than one year. 3. The inflammatory indexes of patients with systemic type were significantly increased, including the increase of WBC and the decrease of HB and serum albumin. 4. Rheumatoid factor RFN, antinuclear antibody Ana, human leukocyte antigen HLA-B 27 and anti-cyclic citrullinated peptide antibody anti-CCPs were found in children with articular type. 5. Serum albumin, as a negative inflammatory marker, was significantly correlated with serum WBCU ESR and HB. Conclusion 1. In this group of JIA cases, the general type was the most common. The children lacking arthritis should be observed for at least one year, and only after other diseases were excluded could the diagnosis of systemic type of JIA be made. 2. The inflammatory index of systemic JIA is more obvious than that of articular type, and serum albumin can be used as a negative inflammation index in clinical evaluation together with serum WBCU ESR and HB. Part two, part three Study on the role of inflammatory reaction in the systemic type of juvenile idiopathic arthritis Purpose The levels of serum TNF- 伪 IL-1 尾 IL-6 and IL-18 in children with SJIA were detected, and the distribution of NLRP3 gene polymorphism in children with SJIA was investigated, and the relationship between NLRP3 gene polymorphism and SJIA was discussed. Method The whole blood and serum of 26 patients with active SJIA were collected. The levels of TNF- 伪 IL-1 尾 and IL-18 in peripheral blood were measured and their expression in children with SJIA was analyzed. The NLRP3 gene was amplified by PCR, and the 9 exons of NLRP3 gene were sequenced. The genotype frequency and allele distribution of each polymorphic locus were analyzed. 39 healthy children were used as control group to detect cytokines. Result 1 the serum levels of TNF- 伪 and IL-1 尾 in children with SJIA were not different from those in the control group. 2. There was no difference in the levels of TNF- 伪 and IL-1 尾 between the children with and without joint symptoms, but the level of IL-18 was higher than that of the control group, and there was no difference between the two groups. 3 the serum IL-6 level was positively correlated with ESR and IL-18 level was positively correlated with ESR. 4. Three SNPs, rs35829419CA, rs7525979 CTand rs3806268GA, were found in the NLRP3 gene of children with SJIA. There was no difference in gene frequency, genotype and population distribution among 5, 3 SNP loci. Conclusion 1. The levels of IL-6 and IL-18 in peripheral blood were correlated with inflammatory markers such as ESR WBC, which indicated the active state of the disease. 2 whether the NLRP3 gene is the susceptible gene of SJIA need further study.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R725.9

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