Cunningham Madeleine W
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Biomedical Research Center , Oklahoma City, OK , USA.
Int Rev Immunol. 2014 Jul-Aug;33(4):314-29. doi: 10.3109/08830185.2014.917411. Epub 2014 Jun 3.
The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and how immune responses against group A streptococci influence autoimmunity and inflammatory responses in the heart and brain.
A组链球菌，即化脓性链球菌，及其与自身免疫后遗症的关联，已获得了新的认识水平。研究支持这样的假说：A组链球菌与心脏或大脑之间的分子模拟在风湿热的免疫反应导向中很重要。本文对风湿性心脏炎、 Sydenham舞蹈病以及一组新的称为与链球菌感染相关的小儿自身免疫性神经精神障碍的行为障碍进行了综述，同时考虑了自身抗体和T细胞反应，以及心脏、大脑与A组链球菌之间分子模拟的作用，还有免疫反应如何促成疾病的致病机制。在风湿性心脏炎中，研究调查了人类单克隆自身抗体和T细胞克隆的交叉反应性及其导致风湿性心脏病瓣膜损伤的机制。尽管对A组链球菌疾病或免疫模型的人类和动物血清研究对于提供分子模拟及其在风湿热发病机制中的作用线索至关重要，但对人类单克隆自身抗体的研究为针对瓣膜的抗体如何激活瓣膜内皮并导致T细胞浸润提供了重要见解。在风湿性心脏炎大鼠模型中被动转移抗链球菌T细胞系说明了CD4 + T细胞对瓣膜的影响。尽管几十年来Sydenham舞蹈病一直被认为是风湿热的神经表现，但自身免疫与行为的结合是一个相对较新的概念，将大脑、行为和神经精神障碍与链球菌感染联系起来。在Sydenham舞蹈病中，人类单克隆抗体及其在转基因小鼠中的表达已将自身免疫与中枢多巴胺途径以及基底神经节中的多巴胺受体和多巴胺能神经元联系起来。综上所述，所综述的研究为理解链球菌后遗症以及针对A组链球菌的免疫反应如何影响心脏和大脑中的自身免疫和炎症反应提供了基础。
