Department of Pediatrics, Yonsei University Wonju College of Medicine, Wonju, Korea.
Clin Exp Rheumatol. 2011 Jul-Aug;29(4):743-50. Epub 2011 Sep 1.
Various genetic variants of inhibitory immune signals have been suspected as feasible causes of Kawasaki disease (KD). We investigated the associative role of programmed death-1 (PD-1) gene in the pathogenesis of KD by injecting bacilli Calmette Guérin (BCG) to PD-1 gene knockout (PD-1KO) mice.
In order to induce KD-like clinical manifestations in young PD-1KO mice, intradermal injection of the bacilli Calmette Guérin (BCG) was performed twice on the abdominal skin with a 4-week interval. For defining the role of BCG, heat shock protein (HSP) 65 was challenged. In addition, Staphylococcus aureus was adopted as a microorganism that does not contain HSP65 structure. One month after the second injection, heart, liver, and kidneys were removed and examined.
PD-1KO mice showed KD-like features including prolonged fever for more than 5 days, erythematous swelling on soles, tail skin desquamation, and gallbladder (GB) hydrops. Inflammatory cell aggregation and intimal proliferation in at least more than one coronary artery was found in all PD-1KO mice whereas scanty coronary lesion was found in wild type (WT) mice. When the PD-1KO mice were injected twice with HSP65, coronary arterial lesions similar to those seen after BCG injection were observed. Inflammatory reactions in other organs including hepatic arteries, renal arteries, and biliary arteries were also observed in PD-1KO mice.
Our data suggest that PD-1 gene may be one of the genetic predispositions of KD and antigens containing HSP65 structure could be a triggering factor of KD by our animal model of KD.
抑制性免疫信号的各种遗传变异被怀疑是川崎病（KD）的可行病因。我们通过向程序性死亡-1（PD-1）基因敲除（PD-1KO）小鼠注射卡介苗（BCG）来研究 PD-1 基因在 KD 发病机制中的关联作用。
为了在年轻的 PD-1KO 小鼠中诱导类似于 KD 的临床表现，在腹部皮肤进行了两次 BCG 皮内注射，间隔 4 周。为了确定 BCG 的作用，挑战了热休克蛋白（HSP）65。此外，采用不含 HSP65 结构的金黄色葡萄球菌作为微生物。第二次注射一个月后，取出心脏、肝脏和肾脏进行检查。
PD-1KO 小鼠表现出类似于 KD 的特征，包括发热超过 5 天、脚底红斑肿胀、尾部皮肤脱皮和胆囊（GB）积水。所有 PD-1KO 小鼠均发现至少一条以上冠状动脉有炎症细胞聚集和内膜增生，而野生型（WT）小鼠仅发现少量冠状动脉病变。当 PD-1KO 小鼠两次注射 HSP65 时，观察到类似于 BCG 注射后所见的冠状动脉病变。PD-1KO 小鼠的其他器官也观察到炎症反应，包括肝动脉、肾动脉和胆管。
我们的数据表明，PD-1 基因可能是 KD 的遗传易感性之一，并且含有 HSP65 结构的抗原可能是我们 KD 动物模型中 KD 的触发因素。
