Does Streptococcal Pyrogenic Exotoxin-C Trigger the Onset of Kawasaki Disease? -Association between Superantigens and Autoantibody against Vascular Smooth Muscle Cells-

Abstract

I) T cell receptor (TCR) usage We investigated TCR usage and antibody responses to streptococcal pyrogenic exotoxin-C (SPE-C) in order to determine whether an association exists between SPE-C and the onset of Kawasaki disease (KD). Patients and Method Fifty-four patients with KD were studied. Analysis of TCR usage was performed by adaptor-ligation PCR and microplate hybridization assay. Serum levels of antibody against SPE-C were assessed by ELISA using purified recombinant protein. Results Forty (74.1%) of the patients with KD showed significant polyclonal activation of Vβ2- and/or Vβ-6.5-bearing T cells. In 22 of 35 paired patients with KD, serum levels of anti-SPE-C antibodies (IgM) in the convalescent phase were lower than those in the acute phase. II) Detection of autoantibodies against vascular smooth muscle cells To investigate the pathogenesis of vasculitis in KD, we tested for the presence of autoantibodies against vascular smooth muscle cells in the patients. Patients and Methods Sera from 48 patients with KD were examined for reactivity with both coronary arterial wall tissues and cultured smooth muscle cells (CSMC) derived from human coronary artery, using immunofluorescence and Western immunoblotting. Results Sera from 16 of 48 patients with KD gave positive immunoreactions with the smooth muscle cells of coronary artery with anti-human IgA antibodies. Western immunoblotting revealed positive reactions of sera from 15 of 34 and 10 of 31 patients with KD against a 70-kDa protein from CSMC with IgA and IgM antibodies, respectively. Positive immunoreactivity of sera from KD patients was detected more frequently in patients with coronary arterial lesions (CAL) than in those without CAL (p <0.05). Conclusions These results suggest that an association may exist between SPE-C and the onset of KD. In addition, autoantibody against vascular smooth muscle cells may cause systemic vasculitis in KD.