Immunogenetics of Kawasaki disease
Immunogenetics of Kawasaki disease
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DOI：
10.1007/s12016-020-08783-9
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发表时间：
2020-08-01
影响因子：
9.1
通讯作者：
Singh, Surjit
中科院分区：
文献类型：
--
作者：
Kumrah, Rajni;Vignesh, Pandiarajan;Singh, Surjit
川崎是一种影响幼儿的中血管炎。尽管在过去的50年里进行了广泛的研究，但KD的病因仍然是一个谜。风型的季节性变化与日本川崎病的流行有关。流行病学聚集性疾病的发生、季节性变化和非常低的复发风险表明KD是由传染性病原体引发的。受影响组织中寡克隆伊加反应的鉴定表明抗原驱动的炎症。最近在支气管纤毛上皮细胞质中发现的病毒抗原也支持感染是KD的主要触发因素。提示KD遗传基础的指标包括东北亚人群中的高患病率、兄弟姐妹中的高风险以及病例的家族发生。先天性和适应性免疫反应失调在KD的急性期很明显。除了冠状动脉壁炎症外，内皮功能障碍和受损的血管重塑有助于冠状动脉异常（CAA）和血栓形成的发展。某些涉及免疫效应子功能的细胞内信号传导途径中的遗传畸变被发现与KD易感性增加和冠状动脉异常（CAA）的发生相关。通过全基因组关联研究（GWAS）和连锁研究（GWLS）已经确定了几个易感基因。在KD中研究的基因可分为4大类-增强的T细胞活化（ITPKC、ORAI 1、STIM 1）、失调的B细胞信号传导（CD 40、BLK、FCGR 2A）、减少的细胞凋亡（CASP 3）和改变的转化生长因子β信号传导（TGFB 2、TGFBR 2、MMP、SMAD）。该综述旨在强调与KD易感性增加相关的几种遗传风险因素的作用。
Kawasaki disease (KD) is a medium vessel vasculitis that affects young children. Despite extensive research over the last 50 years, the etiology of KD remains an enigma. Seasonal change in wind patterns was shown to have correlation with the epidemics of KD in Japan. Occurrence of disease in epidemiological clusters, seasonal variation, and a very low risk of recurrence suggest that KD is triggered by an infectious agent. The identification of oligoclonal IgA response in the affected tissues suggests an antigen-driven inflammation. The recent identification of a viral antigen in the cytoplasm of bronchial ciliated epithelium also favors infection as the main trigger for KD. Pointers that suggest a genetic basis of KD include a high disease prevalence in North-East Asian populations, a high risk among siblings, and familial occurrence of cases. Dysregulated innate and adaptive immune responses are evident in the acute stages of KD. In addition to the coronary wall inflammation, endothelial dysfunction and impaired vascular remodeling contribute to the development of coronary artery abnormalities (CAAs) and thrombosis. Genetic aberrations in certain intracellular signaling pathways involving immune effector functions are found to be associated with increased susceptibility to KD and development of coronary artery abnormalities (CAAs). Several susceptible genes have been identified through genome-wide association studies (GWAS) and linkage studies (GWLS). The genes that are studied in KD can be classified under 4 major groups-enhanced T cell activation (ITPKC,ORAI1,STIM1), dysregulated B cell signaling (CD40,BLK,FCGR2A), decreased apoptosis (CASP3), and altered transforming growth factor beta signaling (TGFB2,TGFBR2,MMP,SMAD). The review aims to highlight the role of several genetic risk factors that are linked with the increased susceptibility to KD.