Sitaram Bhartia Institute of Science and Research, B-16, Mehrauli Institutional Area, New Delhi 110016, India.
Nat Rev Cardiol. 2013 Mar;10(3):171-7. doi: 10.1038/nrcardio.2012.197. Epub 2013 Jan 15.
Rheumatic fever is one of the most-neglected ailments, and its pathogenesis remains poorly understood. The major thrust of research has been directed towards cross-reactivity between streptococcal M protein and myocardial α-helical coiled-coil proteins. M protein has also been the focus of vaccine development. The characteristic pathological findings suggest that the primary site of rheumatic-fever-related damage is subendothelial and perivascular connective tissue matrix and overlying endothelium. Over the past 5 years, a streptococcal M protein N-terminus domain has been shown to bind to the CB3 region in collagen type IV. This binding seems to initiate an antibody response to the collagen and result in ground substance inflammation. These antibodies do not cross-react with M proteins, and we believe that no failure of immune system and, possibly, no molecular mimicry occur in rheumatic fever. This alternative hypothesis shares similarity with collagen involvement in both Goodpasture syndrome and Alport syndrome.
风湿热是最容易被忽视的疾病之一，其发病机制仍不清楚。研究的主要重点是链球菌 M 蛋白与心肌α-螺旋卷曲螺旋蛋白之间的交叉反应。M 蛋白也是疫苗开发的重点。特征性的病理发现表明，风湿热相关损伤的主要部位是内膜下和血管周围的结缔组织基质和覆盖的内皮。在过去的 5 年中，已经证明链球菌 M 蛋白的 N 端结构域与 IV 型胶原的 CB3 区域结合。这种结合似乎启动了对胶原的抗体反应，并导致基质炎症。这些抗体与 M 蛋白不发生交叉反应，我们认为风湿热不会发生免疫系统失败，也可能不会发生分子模拟。这一替代假说与 Goodpasture 综合征和 Alport 综合征中胶原的参与有相似之处。
