T Cell Receptor V-beta Repertoires in Kawasaki Disease and Primary Systemic Vasculitides of Childhood

Abstract

Introduction: Despite conflicting evidence and much debate, superantigenic stimulation of the immune system in Kawasaki disease (KD) remains an attractive hypothesis since there is considerable overlap between the clinical and immunological phenotypes of KD and classical superantigen-mediated diseases such as the toxic shock syndrome. Moreover, although there are limited data in adults suggesting that SAgs may be involved in the initiation of other primary systemic vasculitides, no such data exists for children. Methods: To investigate the possible aetiological role of SAgs, this study examined peripheral blood TCR Vb repertoires in children with KD (n=6), polyarteritis nodosa (PAN, n=23), Wegener's granulomatosis (WG, n=1), and microscopic polyangiitis (MPA, n=1). 20 normal children and 30 children with non-vasculitic inflammatory disease, or recipients of renal allografts served as controls and disease controls respectively. 3 colour FACS analysis of peripheral blood mononuclear cells stained with conjugated monoclonal antibodies to CD3, CD4, CD8, and 17 different Vb families was performed. Results: The mean % of CD4+ T cells bearing Vb2 was significantly increased in the KD group versus controls and disease controls (p=0.03 and p=0.01 respectively). Individual KD patients were also noted to have CD4+ T cell Vb expansions other than Vb2 (Vb5.1 n=2; Vb12 n=1). 60% of the primary systemic vasculitis patients had one or more TCR Vb expansions in the CD4+ lymphocyte population, compared with 30% of the controls (p=0.02-0.05), and 36% of the disease controls (p=0.05-0.1). Unlike KD, however, the pattern of Vb families expanded in individual patients was more diverse, perhaps indicative of the involvement of several different SAgs. Follow-up of 7 primary systemic vasculitis patients demonstrated a normalization of the CD4+ T cell Vb repertoire following induction of remission. Conclusion: Our preliminary data provide indirect evidence for an aetio-pathogenetic role for SAgs in KD and primary systemic vasculitides affecting children.