Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Clin Rev Allergy Immunol. 2020 Aug;59(1):122-139. doi: 10.1007/s12016-020-08783-9.
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.
川崎病（KD）是一种中等大小血管的血管炎，影响幼儿。尽管在过去的 50 年中进行了广泛的研究，但 KD 的病因仍然是个谜。风向的季节性变化与日本 KD 的流行有关。疾病在流行病学群中的发生、季节性变化和极低的复发风险表明 KD 是由感染因子触发的。受影响组织中寡克隆 IgA 反应的出现表明存在抗原驱动的炎症。最近在支气管纤毛上皮细胞的细胞质中发现了一种病毒抗原，也支持感染是 KD 的主要触发因素。提示 KD 具有遗传基础的指标包括东北亚人群的高疾病流行率、兄弟姐妹中的高风险以及家族性病例的发生。在 KD 的急性阶段，先天和适应性免疫反应失调明显。除了冠状动脉壁炎症外，内皮功能障碍和血管重塑受损导致冠状动脉异常（CAA）和血栓形成的发展。涉及免疫效应功能的某些细胞内信号通路中的遗传异常与 KD 的易感性增加和冠状动脉异常（CAA）的发展有关。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 中研究的基因可以分为 4 大类——增强的 T 细胞激活（ITPKC、ORAI1、STIM1）、失调的 B 细胞信号（CD40、BLK、FCGR2A）、减少的细胞凋亡（CASP3）和改变的转化生长因子β信号（TGFB2、TGFBR2、MMP、SMAD）。综述旨在强调与 KD 易感性增加相关的几个遗传危险因素的作用。
