Analysis of signaling via Toll-like receptors in Kawasaki disease

川崎是一种以冠状动脉瘤形成为特征的儿童急性发热性疾病。由于KD的流行呈波浪式，且家族发病率高，因此认为其是由感染性病原体引起的。由于KD患儿外周血中B细胞水平增加和功能障碍，我们研究了KD患儿和细菌或病毒感染患儿B细胞中分化簇180（CD 180）（一种toll样受体同源物）的表达。CD 180阳性B细胞百分率在KD组和病毒感染组均显著高于细菌感染组和健康对照组（P<0.05）。以平均荧光强度（MFI）与细菌感染的比值（0.841 ± 0.315）比较CD 180的表达水平，KD组（1.366±0.443：P=0.0072）和病毒感染组（1.391± 0.307：P=0.0191）CD 180的表达水平也显著上调。为了阐明病毒感染对CD 180表达的影响，B细胞用聚肌苷酸[poly（IC）]刺激，a.合成的双链RNA。Poly（IC）在蛋白质和信使RNA水平均明显增强体外B细胞中CD 180的表达。CD180表达与CAL形成的几个危险因素之间的关系，没有危险因素与CD180的表达水平相关。但CD 180阳性B细胞在有CAL形成的KD患者中所占比例极高。这些结果表明，在KD或病毒感染患者中，B细胞CD 180表达上调可能涉及类似的机制

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