Analysis of signaling via Toll-like receptors in Kawasaki disease

川崎病（Kawasaki disease， KD）是一种以冠状动脉动脉瘤形成为特征的儿童急性发热性疾病。由于该病流行频次大，家族性发病率高，因此认为该病是由感染因子引起的。由于报道KD患儿外周血B细胞水平升高和功能障碍，我们研究了KD患儿和细菌或病毒感染患儿B细胞中toll样受体同源物CD180的表达。KD、病毒感染患儿CD180阳性B细胞比例明显高于细菌感染患儿和健康对照组（P<0.05）。以细菌感染患儿的平均荧光强度（MFI）比（0.841±0.315）比较CD180表达水平，KD患儿（1.366±0.443:P=0.0072）和病毒感染患儿（1.391±0.307:P=0.0191） CD180表达水平也显著上调。为了阐明病毒感染对CD180表达的影响，我们用合成的双链RNA poly （IC）刺激B细胞。Poly（IC）在体外B细胞中明显增强CD180蛋白和信使RNA水平的表达。CD180表达与CAL形成的几个危险因素之间的关系，没有一个危险因素与CD180的表达水平相关。但CD180阳性B细胞的百分比非常高的KD患者显示CAL形成。这些结果表明，类似的机制可能参与了KD或病毒感染患者B细胞CD180表达的上调

Kawasaki disease (KD) is an acute febrile illness in childhood characterized by the formation of aneurysms in coronary arteries. It is believed that KD is caused by infectious agents because of its epidemic waves and high incidence of familial occurrence. Because an increase in the levels and dysfunction of B cells in peripheral blood was reported in KD, we investigated the expression of cluster of differentiation 180 (CD180), a toll-like receptor homologue, in the B cells of children with KD, and in those with bacterial or viral infections. The percentages of CD180 positive B cells were significantly higher in children with KD or viral infections than in those with bacterial infections or in healthy controls (P<0.05). When the expression levels of CD180 were compared by using the mean fluorescent intensity (MFI) ratio of patients to bacterial infection (0.841 ± 0.315), the level of CD180 expression was also significantly up-regulated in children with KD (1.366±0.443 : P=0.0072) or viral infections (1.391± 0.307 : P=0.0191). To clarify the effect of viral infection on the expression of CD180, B cells were stimulated with poly inosinic-cytidyric acid [poly (IC)], a. synthetic double-stranded RNA. Poly(IC) clearly enhanced CD180 expression in B cells in vitro, both at the protein and messenger RNA levels. The association between the CD180 expression and several risk factors for CAL formation, none of risk factors were associated with the expression level of CD180. But the percentage of CD180 positive B cells was extremely high in KD patients displaying CAL formation. These results suggest that similar mechanisms may be involved in the up-regulation of B cell CD180 expression in patients with either KD or viral infections