Oligoclonal IgA response in the vascular wall in acute Kawasaki disease

Kawasaki Disease (KD) is a potentially fatal acute vasculitis of childhood. Although KD is the leading cause of acquired heart disease in children in developed nations, its pathogenesis remains unknown. We previously reported the novel observation that IgA plasma cells infiltrate the vascular wall i n acute KD. We have now examined the clonality of this IgA response in vasc ular tissue from three fatal cases of KD to determine whether it is oligocl onal, suggesting an Ag-driven process, or polyclonal, suggesting nonspecifi c B cell activation or a response to a superantigen. We first sequenced VDJ junctions of 44 alpha genes isolated from a primary, unamplified KD vascul ar cDNA library. Five sets of clonally related alpha sequences were identif ied, comprising 34% (15 of 44) of the isolated alpha sequences. Furthermore , point mutations consistent with somatic mutation were detected in the rel ated sequences. Next, using formalin-fixed coronary arteries from two addit ional fatal KD cases, we sequenced VDJ junctions of alpha genes isolated by RT-PCR, and a restricted pattern of CDR3 usage was observed in both. We co nclude that the vascular IgA response in acute KD is oligoclonal. The ident ification of an oligoclonal IgA response in KD strongly suggests that the i mmune response to this important childhood illness is Ag-driven.