Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/36131
標題: 風濕疾病之自體抗體與免疫遺傳基因之關聯性探討
Investigation of the correlation between autoantibodies and immunogenetics in rheumatic diseases
作者: 林芳如
Lin, Fang-Ju
關鍵字: Rheumatic rheumatoid;類風濕性關節炎;idiopathic infalmmatory myopathies;autoantibodies;特發性發炎性肌炎病變;自體抗體
出版社: 生物科技學研究所
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摘要: 
類風濕性關節炎(Rheumatoid arthritis;RA)與特發性發炎性肌炎病變(Idiopathic inflammatory myopathies,IIM)都屬於風濕疾病。類風濕性關節炎是一種廣泛且頑固的慢性疾病,且會引起全身性的關節腫脹、疼痛及損壞。特發性發炎性肌病變則是一群以骨骼肌的近肢體無力與非化膿性發炎為特徵的疾病。本研究藉由中國人類風濕性關節炎與特發性發炎性肌炎病變患者之自體抗體的偵測與分析,進一步探討風濕疾病的自體抗體與免疫遺傳基因的關聯性。本實驗純化人類6-磷酸葡萄糖異構酵素為抗原,以ELISA偵測類風濕關節炎患者、多種自體免疫疾病患者及正常人之血清中抗6-磷酸葡萄糖異構酵素抗體之力價高低,顯示在類風濕關節炎及陣發性風濕症(PMRA)之病患血清中,存在較高的抗6-磷酸葡萄糖異構酵素抗體。將此抗原製備多株抗體,利用免疫組織染色法,於類風濕關節炎及陣發性風濕症關節滑膜組織偵測高濃度的6-磷酸葡萄糖異構酵素。進一步探討6-磷酸葡萄糖異構酵素抗體陽性之類風濕性關節炎與陣發性風濕症患者之免疫遺傳基因,結果顯示6-磷酸葡萄糖異構酵素抗體陽性之類風濕性關節炎與陣發性風濕症患者出現HLA-DR4遺傳基因的發生率明顯高於正常對照組,但是類風濕性關節炎患者出現HLA-DR3遺傳基因的發生率明顯低於正常對照組。另外針對中國人特發性發炎性肌炎病變,建立放射免疫沉降電泳法偵測自體抗體的存在與種類,進一步探討其臨床表徵、自體抗體與免疫遺傳基因的相關性。本研究的結果顯示,特發性發炎性肌病變中國患者,其血清存在自體抗體anti-Jo-1抗體陽性比率最高 (17.8%),其次為anti-EJ抗體 (7.0%),而且多發性肌炎患者具有anti-SRP抗體與anti-Jo-1抗體之機率明顯高於皮肌炎患者。針對自體免疫抗體與臨床表徵的相關性探討,我們的研究結果顯示anti-Jo-1抗體陽性與抗合成酶症候群的表徵有顯著的正相關。然而肌炎相關性抗體,包括anti-SSA/Ro抗體及anti-SSB/La抗體則與臨床表徵無顯著關聯。特發性發炎性肌炎病變之HLA基因多型性,在不同種族有所差異性,本實驗的結果顯示特發性發炎性肌病變患者之HLA-DRB1*08遺傳基因的發生率明顯高於正常對照組,但卻沒有發現中國人患者具有免疫遺傳的保護因子。綜言之,本實驗的研究結果顯示中國患者的類風濕性關節炎與6-磷酸葡萄糖異構酵素抗體,及特發性發炎性肌炎病變之特異性肌炎抗體、臨床表徵與免疫遺傳基因有顯著關聯。

Rheumatic diseases included rheumatoid arthritis (RA) and idiopathic inflammatory myopathies (IIM). Rheumatoid arthritis is a systemic chronic inflammatory joint disease that eventually leads to the destruction of the joint architecture. Idiopathic inflammatory myopathies are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and inflammatory cell infiltrates in muscle. In this study, we detected and analyzed the autoantibodies of Chinese patients with RA and IIM. PGI recombinant protein was purified from growing E. coli harboring the CB1821 by DEAE and SP column. It was used to examine the presence of antibodies to PGI in serial diluted sera from patients with RA, other autoimmune diseases and healthy controls by ELISA. The data indicated that there are higher concentration of anti-PGI IgG in the sera of the RA and palindromic rheumatism (PMRA). We prepared the polyclonal antibody of human PGI. Fresh-frozen tissues in these groups were obtained and immunohistochemical analyzed on cryostat tissue sections done with polyclonal antibody to human PGI. Immunohistochemistry of RA and PMRA synovium showed high concentration of PGI on the synovium. To analyze the HLA DRB1 genotype, we found the associations with HLA-DR4 on the anti-PGI-positive in RA and PMRA patients, To detect the autoantibodies, we established the electrophoresis system of the radioimmunoprecipitation. Anti-Jo-1 antibodies were the most common and anti-EJ antibodies were the second. The positive ratio of anti-SRP and anti-Jo-1 antibodies in polymyositis was obviously higher than in dermatomyositis. This study also showed the positive correlation between anti-Jo-1 antibodies and anti-synthetase syndrome. The myositis-associated antibodies, including anti-SSA/Ro and anti-SSB/La, were not correlated with clinical syndrome. The HLA gene polymorphisms in IIM were different in various ethnic groups. The results showed that HLA-DRB1*08 in IIM was obviously higher than in normal controls, but we couldn't find the protective factors in Chinese. In all, this study showed the significant correlation between RA and anti-PGI antibodies, IIM and myositis-specific antibodies, clinic symptoms and immunogenetics in Chinese.
URI: http://hdl.handle.net/11455/36131
其他識別: U0005-2908200611465200
Appears in Collections:生物科技學研究所

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