本文選題：幼年特發(fā)性關(guān)節(jié)炎 + 關(guān)節(jié)炎�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2014年博士論文

【摘要】：第一部分 幼年特發(fā)性關(guān)節(jié)炎189例臨床分析 目的 探討幼年特發(fā)性關(guān)節(jié)炎(JIA)的臨床表現(xiàn)、分類(lèi)及實(shí)驗(yàn)室檢查特點(diǎn),以及炎癥指標(biāo)在臨床評(píng)價(jià)中的作用。 方法 總結(jié)2003年1月～2013年6月我院住院收治的189例JIA患兒臨床癥狀、體征、及實(shí)驗(yàn)室檢查資料,以2001年國(guó)際風(fēng)濕病學(xué)聯(lián)盟兒科專(zhuān)家組制訂的JIA標(biāo)準(zhǔn)進(jìn)行分類(lèi),并對(duì)JIA患兒的臨床表現(xiàn)、實(shí)驗(yàn)室檢查進(jìn)行回顧性分析。 結(jié)果 1、本組JIA患兒男100例,女89例。其中全身型119例(62.9%),少關(guān)節(jié)型13例(6.9%),多關(guān)節(jié)型(RF陽(yáng)性)16例(8.5%),多關(guān)節(jié)型(RF陰性)15例(7.9%),與附著點(diǎn)炎性反應(yīng)相關(guān)的關(guān)節(jié)炎13例(6.9%),銀屑病性關(guān)節(jié)炎3例(1.6%),未分類(lèi)的關(guān)節(jié)炎10例(5.3%)。 2、全身型臨床表現(xiàn)為發(fā)熱、皮疹、淋巴結(jié)大、肝大和(或)脾大等非特異性癥征,病程1年以上者未再發(fā)現(xiàn)腫瘤及其他疾病。 3、全身型患者炎癥指標(biāo)升高更明顯,包括血WBC升高、ESR增快以及Hb和血清白蛋白的降低。 4、關(guān)節(jié)型患兒可見(jiàn)類(lèi)風(fēng)濕因子(RF)、抗核抗體(ANA)、人類(lèi)白細(xì)胞抗原(HLA)—B27和抗環(huán)瓜氨酸肽抗體(anti-CCP)等抗體不同程度的陽(yáng)性。 5、血清白蛋白作為負(fù)性炎癥指標(biāo)與血WBC、ESR和Hb明顯相關(guān)。 結(jié)論 1、本組JIA病例中以全身型為最多見(jiàn),對(duì)缺少關(guān)節(jié)炎表現(xiàn)的患兒應(yīng)觀(guān)察至少1年以上、排除其他疾病后才能確診JIA全身型； 2、全身型JIA患者的炎癥指標(biāo)較關(guān)節(jié)型更明顯,血清白蛋白可與血WBC、ESR和Hb一起作為負(fù)性炎癥指標(biāo)用于臨床評(píng)估。 第二、三部分 炎癥反應(yīng)在幼年特發(fā)性關(guān)節(jié)炎全身型的作用研究 目的 檢測(cè)SJIA患兒血清TNF-α、IL-1β、IL-6及IL-18等炎癥因子水平,了解NLRP3基因多態(tài)性在SJIA患兒中的分布情況,探討NLRP3基因多態(tài)性與SJIA的關(guān)系。 方法 收集我院確診并長(zhǎng)期我院隨診的26例活動(dòng)期SJIA患兒全血及血清。外周血清測(cè)定TNF-α、IL-1β、IL-6及IL-18水平,分析其在SJIA患兒中的表達(dá)情況。全血提取DNA, PCR法擴(kuò)增NLRP3基因,測(cè)定NLRP3基因9個(gè)外顯子序列,分析各多態(tài)性位點(diǎn)基因型頻率、等位基因分布與SJIA發(fā)病的關(guān)系。39名健康兒童作為對(duì)照組留取血清測(cè)定細(xì)胞因子。 結(jié)果 1、SJIA患兒血清中TNF-α、IL-1β水平與對(duì)照組相比無(wú)差別。 2、有關(guān)節(jié)癥狀和無(wú)關(guān)節(jié)癥狀的患兒相比TNF-α、IL-1β水平無(wú)差異,而IL-6、IL-18水平均高于對(duì)照組,兩組間無(wú)差異。 3、SJIA患兒血清IL-6水平與ESR呈正相關(guān),IL-18水平與WBC、ESR呈正相關(guān)。 4、在SJIA患兒NLRP3基因中發(fā)現(xiàn)3個(gè)SNP, rs35829419CA, rs7525979CT, rs3806268GA。 5、3個(gè)SNP位點(diǎn)的基因頻率、基因型與人群分布無(wú)差異。 結(jié)論 1、外周血IL-6及IL-18水平與ESR、WBC等炎癥指標(biāo)相關(guān),能夠提示疾病的活動(dòng)狀態(tài)。 2、NLRP3基因是否為SJIA發(fā)病的易感基因仍需進(jìn)一步探討。
[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- 偽 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- 偽 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- 偽 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- 偽 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.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R725.9

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