探討血液循環系統中的細菌感染引發自體抗體生成之機制

Abstract

感染可能引發風溼熱、吉蘭-巴雷氏症狀群等自體免疫疾病。本實驗室先前的研究指出，感染性心內膜炎及擴散性全身性感染患者體內含有抗雙股去氧核糖核酸抗體。當大鼠經由靜脈感染轉糖鏈球菌後，體內會產生抗雙股去氧核糖核酸抗體。脾臟對於清除血液中的細菌及產生抗體扮演一定的角色；因此，我們假設血液中的細菌可能引發脾臟產生自體抗體。我們發現，當小鼠經由靜脈感染後，在5至7天內能產生抗雙股去氧核糖核酸抗體；利用脾臟被切除的小鼠進行同樣的實驗，發現小鼠體內抗雙股去氧核糖核酸抗體的量下降，顯示血液中的細菌能促使脾臟產生自體抗體。我們發現純化的抗雙股去氧核糖核酸抗體和轉糖鏈球菌的表面蛋白: 葡餹基轉移酶B有交叉反應。另外，紅斑性狼蒼患者體內通常具有大量的抗雙股去氧核糖核酸抗體，我們發現有一種核醣體蛋白: L7/L12在紅斑性狼蒼患者體內可能無法誘發產生抗雙股去氧核糖核酸抗體。以上結果顯示血液循環系統中的細菌感染能使脾臟產生自體抗體，而葡餹基轉移酶B及L7/L12可能產生交叉反應促使自體抗體的產生。

Infections play roles in the induction of autoimmune diseases, including rheumatic fever and Guillain–Barré syndrome. Our previous data showed that autoantibodies such as anti-dsDNA antibodies can be found in patients with infective endocarditis and disseminated systemic infection. The anti-dsDNA antibodies can be induced in rat intravenously infected with Streptococcus mutans. Spleen plays roles in the clearance of circulating bacteria and antibody production; therefore, we hypothesized spleen may produce autoantibodies induced by circulating bacteria. We found that anti-dsDNA antibodies could be induced within 5-7 days after intravenous infection in the mouse model. The anti-dsDNA IgG levels were decreased in the mice with splenectomy, suggesting spleen can produce autoantibodies induced by circulating bacteria. The purified anti-dsDNA antibodies can cross-react with a S. mutans surface protein, glucosyltransferase B. On the other hand, systemic lupus erythematosus patients usually have high levels of anti-dsDNA antibodies. We found that a ribosomal protein named L7/L12 may not be an inducer of anti-dsDNA antibodies in SLE patients. Taken together, spleen play roles in autoantibody production caused by circulating infection, and the GtfB and L7/L12 may induce the cross-reactive autoantibody production.