Guilherme L, Ramasawmy R, Kalil J
Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil.
Scand J Immunol. 2007 Aug-Sep;66(2-3):199-207. doi: 10.1111/j.1365-3083.2007.01974.x.
Molecular mimicry between streptococcal and human proteins is considered as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). Here, we present a review of the genetic susceptibility markers involved in the development of RF/RHD and the major immunopathological events underlying the pathogenesis of RF and RHD. Several human leucocyte antigen (HLA) class II alleles are associated with the disease. Among these alleles, HLA-DR7 is predominantly observed in different ethnicities and is associated with the development of valvular lesions in RHD patients. Cardiac myosin is one of the major autoantigens involved in rheumatic heart lesions and several peptides from the LMM (light meromyosin) region were recognized by peripheral and intralesional T-cell clones from RF and RHD patients. The production of TNF-alpha and IFN-gamma from heart-infiltrating mononuclear cells suggests that Th-1 type cytokines are the mediators of RHD heart lesions while the presence of few interleukin-4 producing cells in the valve tissue contributes to the maintenance and progression of the valvular lesions.
链球菌与人类蛋白质之间的分子模拟被认为是导致风湿热（RF）和风湿性心脏病（RHD）自身免疫的触发因素。在此，我们综述了参与RF/RHD发病的遗传易感性标志物以及RF和RHD发病机制背后的主要免疫病理事件。几种人类白细胞抗原（HLA）II类等位基因与该疾病相关。在这些等位基因中，HLA-DR7在不同种族中均有较高比例出现，且与RHD患者瓣膜病变的发生有关。心肌肌球蛋白是风湿性心脏病变中主要的自身抗原之一，来自RF和RHD患者的外周和病变内T细胞克隆识别了来自轻酶解肌球蛋白（LMM）区域的几种肽段。心脏浸润单核细胞产生的肿瘤坏死因子-α和干扰素-γ表明，Th-1型细胞因子是RHD心脏病变的介质，而瓣膜组织中少量产生白细胞介素-4的细胞的存在有助于瓣膜病变的维持和进展。
