Rheumatic Fever and Rheumatic Heart Disease: Cellular Mechanisms Leading Autoimmune Reactivity and Disease
Rheumatic Fever and Rheumatic Heart Disease: Cellular Mechanisms Leading Autoimmune Reactivity and Disease
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DOI：
10.1007/s10875-009-9332-6
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发表时间：
2010-01-01
影响因子：
9.1
通讯作者：
Kalil, Jorge
中科院分区：
文献类型：
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作者：
Guilherme, Luiza;Kalil, Jorge
风湿热 (RF) 是一种由革兰氏阳性菌化脓性链球菌引起的自身免疫性疾病，易感儿童因咽喉感染未经治疗而引起。该疾病表现为多关节炎、心脏炎、舞蹈病、边缘红斑和/或皮下结节。心脏炎是最严重的并发症，发生在 30% 至 45% 的 RF 患者中，并导致慢性风湿性心脏病 (RHD)，其特征是进行性和永久性瓣膜病变。在这篇综述中，我们将重点关注导致该疾病易感性的基因，以及急性风湿热发作期间针对化脓性链球菌的先天性和适应性免疫反应，从而导致 RHD 自身免疫反应。该疾病是由基因决定的，一些人类白细胞抗原 II 类等位基因与易感性有关。据报道，TNF-α 和甘露聚糖结合凝集素基因的其他单核苷酸多态性与 RF/RHD 相关。 T 细胞在 RHD 心脏病变中发挥重要作用。几种自身抗原已经被鉴定出来，包括心肌肌球蛋白表位、波形蛋白和其他细胞内蛋白。在心脏组织中，抗原驱动的寡克隆 T 细胞扩增可能是风湿性心脏病变的效应器。这些细胞是 CD4(+) 并产生炎症细胞因子（TNF α 和 IFN γ）。分子拟态是介导链球菌抗原和人类蛋白质之间交叉反应的机制。阐明与 Th1、Th2 和 Th17 细胞募集相关的趋化因子及其受体，以及原位 T 调节细胞的功能，无疑将有助于描绘导致 RHD 的心脏病变过程的真实情况。
Rheumatic fever (RF) is an autoimmune disease caused by the gram-positive bacteria Streptococcus pyogenes that follows a nontreated throat infection in susceptible children. The disease manifests as polyarthritis, carditis, chorea, erythema marginatum, and/or subcutaneous nodules. Carditis, the most serious complication, occurs in 30% to 45% of RF patients and leads to chronic rheumatic heart disease (RHD), which is characterized by progressive and permanent valvular lesions. In this review, we will focus on the genes that confer susceptibility for developing the disease, as well as the innate and adaptive immune responses against S. pyogenes during the acute rheumatic fever episode that leads to RHD autoimmune reactions.The disease is genetically determined, and some human leukocyte antigen class II alleles are involved with susceptibility. Other single nucleotide polymorphisms for TNF-alpha and mannan-binding lectin genes were reported as associated with RF/RHD. T cells play an important role in RHD heart lesions. Several autoantigens were already identified, including cardiac myosin epitopes, vimentin, and other intracellular proteins. In the heart tissue, antigen-driven oligoclonal T cell expansions were probably the effectors of the rheumatic heart lesions. These cells are CD4(+) and produced inflammatory cytokines (TNF alpha and IFN gamma).Molecular mimicry is the mechanism that mediated the cross-reactions between streptococcal antigens and human proteins. The elucidation of chemokines and their receptors involved with the recruitment of Th1, Th2, and Th17 cells, as well as the function of T regulatory cells in situ will certainly contribute to the delineation of the real picture of the heart lesion process that leads to RHD.