Development of serum IgM antibodies against superantigens of Staphylococcus aureus and Streptococcus pyogenes in Kawasaki disease

• Published in: Clinical and experimental immunology Vol. 143; no. 3; pp. 427 - 434
• Main Authors: Matsubara, K., Fukaya, T., Miwa, K., Shibayama, N., Nigami, H., Harigaya, H., Nozaki, H., Hirata, T., Baba, K., Suzuki, T., Ishiguro, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2006; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Antibodies, Bacterial - blood; Bacterial Proteins - immunology; Bacterial Toxins - immunology; Biological and medical sciences; Case-Control Studies; Child; Child, Preschool; Clinical Studies; Enterotoxins - immunology; Exotoxins - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunoglobulin G - blood; Immunoglobulin M - blood; Immunoglobulins, Intravenous - therapeutic use; Immunopathology; Infant; Kawasaki disease; Male; Medical sciences; Membrane Proteins - immunology; Mucocutaneous Lymph Node Syndrome - immunology; Mucocutaneous Lymph Node Syndrome - therapy; pathogenesis; serological evidence; Staphylococcus aureus; Staphylococcus aureus - immunology; Streptococcus pyogenes; Streptococcus pyogenes - immunology; superantigen; Superantigens - immunology; toxin; Kawasaki syndrome; Immunopathology; Antibody; Pathogenesis; Cardiovascular disease; Autoimmune disease; Serology; IgM; Vascular disease; Streptococcaceae; Toxin; Immunology; Vasculitis; Kawasaki disease; serological evidence; Systemic disease; Superantigen; Bacteria; Micrococcales; Streptococcus pyogenes; Serum; Micrococcaceae; Staphylococcus aureus
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2006.03015.x

Summary 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.