Matsubara K, Fukaya T, Miwa K, Shibayama N, Nigami H, Harigaya H, Nozaki H, Hirata T, Baba K, Suzuki T, Ishiguro A
Department of Paediatrics, Nishi-Kobe Medical Centre, 5-7-1 Kojidai, Nishi-ku, Kobe 651-2273, Japan.
Clin Exp Immunol. 2006 Mar;143(3):427-34. doi: 10.1111/j.1365-2249.2006.03015.x.
To serologically determine the association of microbial superantigens and the pathogenesis of Kawasaki disease (KD), we conducted a case-control study. Serum IgG and IgM antibodies against staphylococcal enterotoxin A (SEA), SEB, SEC, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxin A (SPEA) were measured by an enzyme-linked immunosorbent assay in 293 serum samples from 65 KD patients on clinical days 1-28 and 120 control samples. The administration of immunoglobulin products, which contain high concentrations of IgG antibodies against all the superantigens, directly elevated antitoxin IgG antibodies in KD patients. In contrast, antitoxin IgM antibodies were not detected in immunoglobulin products. Actually, we found a significant elevation of IgM antibodies against SEA in KD patients in the first (median titre: 0.020, P < 0.01 versus control), second (0.024, P < 0.001), third (0.030, P < 0.001) and fourth (0.038, P < 0.001) weeks, compared to the controls (0.015). Significant differences of IgM antibodies were also true for SEB, TSST-1, and SPEA throughout the first to fourth weeks, and for SEC throughout the second to fourth weeks. The prevalence of KD patients having high IgM titres (> mean + 2SD of control values) to the 5 superantigens was increased with the clinical weeks, and reached 29-43% of KD subjects at the fourth week. This is the first study that describes kinetics of IgM antibodies against superantigens and clarifies the serological significance throughout the clinical course of KD. Our results suggest that multiple superantigens involve in the pathogenesis of KD.
为了通过血清学方法确定微生物超抗原与川崎病（KD）发病机制之间的关联，我们进行了一项病例对照研究。采用酶联免疫吸附测定法检测了65例KD患者在临床第1 - 28天的293份血清样本以及120份对照样本中针对葡萄球菌肠毒素A（SEA）、SEB、SEC、中毒性休克综合征毒素-1（TSST-1）和链球菌致热外毒素A（SPEA）的血清IgG和IgM抗体。含有针对所有超抗原的高浓度IgG抗体的免疫球蛋白产品的使用，直接提高了KD患者的抗毒素IgG抗体水平。相比之下，在免疫球蛋白产品中未检测到抗毒素IgM抗体。实际上，我们发现与对照组（0.015）相比，KD患者在第一周（中位滴度：0.020，与对照组相比P < 0.01）、第二周（0.024，P < 0.001）、第三周（0.030，P < 0.001）和第四周（0.038，P < 0.001）针对SEA的IgM抗体显著升高。在第一周至第四周期间，针对SEB、TSST-1和SPEA的IgM抗体也存在显著差异，在第二周至第四周期间针对SEC的IgM抗体也有显著差异。KD患者中针对这5种超抗原具有高IgM滴度（>对照组均值 + 2SD）的患病率随临床周数增加，在第四周达到KD受试者的29 - 43%。这是第一项描述针对超抗原的IgM抗体动力学并阐明KD整个临床过程中血清学意义的研究。我们的结果表明多种超抗原参与了KD的发病机制。
