The cross reactive antigen in mycobacterium to vascular endothelium : the new mouse model for Kawasaki disease.

川崎病的病因尚不清楚。本病常观察到BOG接种部位硬化。这可能是由于与相关微生物（如非典型分枝杆菌）的重复感染。我们检查了冠状动脉交叉反应性抗原的免疫病理学，该抗原可能具有BOG成分和非典型分枝杆菌的免疫原性。提取了胞内微杆菌（Microbacterium intracellululi，简称cwMI）的细胞壁成分。3周龄雌性小鼠（C57BL/6J）皮下接种BCG或生理盐水。四周后，动物腹腔注射cwMI或生理盐水。BCG+cwMI组小鼠出现冠状动脉炎伴炎性细胞浸润。作为对照，既没有接受生理盐水再加cwMI的动物，也没有接受BOG再加生理盐水的动物发生冠状动脉炎。BCG+cwMI组动物的TNF-a和IFN-g产量显著高于对照组（p<0.05）。经BLAST搜索，心肌梗死AhpC与内皮细胞过氧化物还毒素具有同源性（35%同源性）。静脉注射兔抗过氧化物还蛋白血清也发生冠状动脉炎，导致TNF-a和IFN-g的产生明显高于对照组。这些结果表明，卡介苗、非典型分枝杆菌和内皮成分之间的分子模拟可导致小鼠冠状动脉炎。接种卡介苗后非典型分枝杆菌重复感染可通过对过氧化物还氧蛋白的交叉反应作为自身免疫反应而发生冠状动脉炎。我们的新模型可能阐明川崎病的病因。

The etiology of Kawasaki disease remains unknown. Induration of BOG vaccination site was frequently observed in this disease. This might result from superinfection with the related microbe(s) such as atypical mycobacteria. We have examined the immunopathology to a cross reactive antigen for coronary artery that might share the immunogenisity of a BOG component and atypical mycobacteria.The cell wall components of Microbacterium intracellulare (cwMI) were extracted. Female mice (C57BL/6J) of 3 week-old were inoculated subcutaneously with BCG or saline. Four weeks later, the animals were inoculated intraperitoneally with the cwMI or saline. The animals received BCG followed by cwMI developed coronary arteritis with infiltration of inflammatory cells (BCG+cwMI group). As controls, neither animals received saline followed by cwMI nor those received BOG followed by saline developed coronary arteritis. The animals in the BCG+cwMI group had significantly higher TNF-a and IFN-g production than the control groups (p<0.05). When multiple doses of cwMI were inoculated with BCG-inoculated mice, these cytokine production became more prominent By BLAST search, AhpC of MI had homology to peroxiredoxin of endothelium (35% identity). Intravenous injection with rabbit anti-peroxiredoxin serum also developed coronary arteritis and resulted in significantly higher TNF-a and IFN-g production than the control. These results indicated that molecular mimicry between BCG, atypical mycobacteria and endotherium components lead to the coronary arteritis in mice. Atypical mycobacteria superinfection in individuals who had BCG vaccination might develop coronary arteritis by cross reactive to peroxiredoxin as auto immune reaction. Our new model may clarify the etiology of Kawasaki disease.