對抗共生鏈球菌醣蛋白及嗜中性白血球胞外網狀結構抗體的交叉反應

Abstract

感染可能引起自體免疫疾病，如：風溼熱(rheumatic fever)、Guillain–Barré syndrome。在感染性心內膜炎(infective endocarditis, IE)及擴散性全身性感染(disseminated systemic infection)患者血清中可以偵測到多種自體抗體，如：抗雙股去氧核糖核酸抗體(anti-dsDNA antibodies)和抗磷脂質抗體(anti-phospholipid antibodies)。實驗室先前的研究發現大鼠感染轉糖鏈球菌(S. mutans)後，血清中抗雙股去氧核糖核酸抗體會上升。然而，目前我們仍然不清楚究竟是細菌的何種物質引起自體抗體產生。在本篇研究中，將探討鏈球菌細胞壁表面蛋白是否會引起抗雙股去氧核糖核酸抗體的產生。研究結果發現大鼠靜脈注射鏈球菌細胞壁表面蛋白後，體內抗雙股去氧核糖核酸抗體有明顯增加。而且純化的抗雙股去氧核糖核酸抗體對GtfB/C及60 kDa免疫優勢醣蛋白有交叉反應。並且在GtfB/C及60 kDa免疫優勢醣蛋白致敏的兔子血清中也可以測到抗雙股去氧核糖核酸抗體的存在。另外，大部分系統性紅斑狼瘡(systemic lupus erythematosus, SLE)患者血清會專一地辨認醣化的鏈球菌細胞壁蛋白；而健康捐贈者血清則無反應或僅有弱反應性。綜合以上結果，在大鼠動物實驗當中，鏈球菌細胞壁蛋白參與抗雙股去氧核糖核酸抗體的生成；以及在系統性紅斑狼瘡病患血清中發現抗細菌醣蛋白抗體。

Infection may induce autoimmune diseases such as rheumatic fever and Guillain–Barré syndrome. Various autoantibodies, such as anti-dsDNA antibodies, anti-phospholipid antibodies, can be found in patients with infective endocarditis (IE) and disseminated systemic infection. Our previous works showed that anti-dsDNA antibodies are induced in rats infected with Streptococcus mutans. However, which bacterial components are responsible for autoantibody formation remains unclear. Here, we found that anti-dsDNA antibodies could be induced in rats intravenously injected with streptococcal proteins. Eluted anti-dsDNA antibodies from the rat serum can cross-react with glycosyltransferase B/C (GtfB/C) and 60-kDa immunodominant glycoprotein (IdG60). Sera from rabbits against GtfB/C or IdG60 also can recognize dsDNA rather than sera from autolysin-immunized rabbit. In addition, specific glycosylated streptococcal proteins can be recognized by sera from most of systemic lupus erythematosus patients but not from healthy donors. Therefore, the bacterial glycoproteins may be involved in autoantibody production in disseminated systemic infection or SLE patients.