Vasculitis induced by immunization with Bacillus Calmette-Guerin followed by atypical mycobacterium antigen: a new mouse model for Kawasaki disease
Vasculitis induced by immunization with Bacillus Calmette-Guerin followed by atypical mycobacterium antigen: a new mouse model for Kawasaki disease
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DOI：
10.1111/j.1574-695x.2007.00217.x
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发表时间：
2007-04-01
影响因子：
--
通讯作者：
Takahashi, Hiroaki
中科院分区：
文献类型：
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作者：
Nakamura, Tsuneyuki;Yamamura, Jun-ichi;Takahashi, Hiroaki
川崎病会引起系统性脉管炎。卡介苗(BCG)接种部位的皮损是一种重要的诊断症状。我们推测，感染与卡介苗免疫相关的普遍存在的微生物可能会引起免疫病理反应，从而导致川崎病的发生。小鼠先接种卡介苗，4周后再次接种丰富的非典型分支杆菌胞内分枝杆菌粗提物。接种卡介苗后再接种卡介苗的动物发生冠脉炎，并伴有炎症细胞的渗透，而只接种卡介苗或卡介苗的对照组动物则没有，这表明对分枝杆菌的免疫反应诱导了对血管壁的自身免疫。静脉注射过氧化还蛋白II的抗体也会导致冠脉炎，但前提是事先接种了卡介苗。过氧化还蛋白II是一种血管重塑的调节剂，也是自身免疫性血管炎的靶标。接种卡介苗的动物肿瘤坏死因子-α、单核细胞趋化蛋白1和干扰素-γ的产生显著高于对照组(P<；0.05)。冠状动脉炎症的发生需要卡介苗免疫，提示这些细胞因子可能起重要作用。结果表明，卡介苗诱导原发自身免疫，刺激细胞因子诱导，非典型分枝杆菌感染促进自身免疫，导致冠脉炎。
Kawasaki disease causes systemic vasculitis. The development of skin lesions at the vaccination site with Bacillus Calmette-Guerin (BCG) is an important diagnostic symptom. We hypothesized that infection with ubiquitous microorganisms immunogenically related to BCG might induce an immunopathologic reaction leading to the development of Kawasaki disease. Mice were first inoculated with BCG, and then secondarily inoculated 4 weeks later with crude extract from Mycobacterium intracellulare (cMI), an abundant atypical mycobacterium. Animals inoculated with BCG followed by cMI developed coronary arteritis with infiltration of inflammatory cells, whereas control animals inoculated with only cMI or BCG did not, suggesting that the immune response to the mycobacteria induced autoimmunity to the vascular wall. Intravenous injection with antibodies to peroxiredoxin II, a modulator of vascular remodeling and a suggested target for autoimmune vasculitis, also resulted in coronary arteritis, but only after prior inoculation with BCG. Tumor necrosis factor-alpha, MCP1 and interferon-gamma production were significantly higher in the animals inoculated with BCG than in the control groups (P < 0.05). BCG immunization was required for the development of coronary arteritis, suggesting that these cytokines might play important roles. The results indicate that BCG induces primary autoimmunity and stimulates cytokine induction, and that atypical mycobacterial infection boosts the autoimmunity resulting in coronary arteritis.