Kawasaki's disease (KD) is the most common acute vasculitis of childhood and can lead to significant morbidity secondary to the development of coronary arteritis and aneurysms. The present proposal seeks to determine the potential role of superantigen in the etiology of KD. Our preliminary analysis of 19 patients meeting clinical criteria for KD, as well as studies from other centers, suggests that a superantigen might play a role in some, but not all, patients. Further studies in a larger patient group is necessary before a conclusion can be reached; the studies outlined in this proposal will add the analysis of an anticipated additional 20 KD patients admitted to the Children's Hospital in Cincinnati during the next year. Flow cytometry will be used to analyze peripheral blood lymphocytes (PBL) at presentation and at convalescence (6 weeks), for expansion of specific Vbeta families of T cell receptors (TCR), as well as for expression of the activation markers IL-2 receptor and HLA-DR, and the memory marker CD45RO. mRNA from PBL will also be analyzed by polymerase chain reaction (PCR) for those Vbeta families which cannot be studied by flow cytometry (due to the unavailability of specific monoclonal antibodies). Additional studies will determine the cell populations involved in coronary arteritis in an animal model of vasculitis with some similarities to KD induced by the administration of Lactobacillus casei (L. casei) cell wall extract. These studies will determine whether L. casei contains superantigens which are responsible for this disease, the cell population(s) responsible for vasculitis, whether TCR expression in the vasculitic lesions differs from that in the periphery, and whether T cells in the vasculitic lesions are clonal or polyclonal in nature. These studies should lead to a clarification of the potential role of superantigen in the etiology of KD resulting in a better understanding of the pathophysiology of this important childhood illness.
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