Local production of IgA in vascular tissue in fatal Kawasaki Syndrome. • 761

Abstract

The etiology and pathogenesis of KS remain unknown. To search for an etiologic agent, we have made an oligo dT-primed, directional λZAP expression cDNA library from vascular tissue at the aorto-iliac junction of a patient with fatal acute KS (illness day 13). We screened the library with convalescent patient serum followed by anti-human immunoglobulin. Surprisingly, the library contains many clones (0.1%) which are detected with anti-human immunoglobulin alone, indicating that they produce immunoglobulin(Ig) and that there is local synthesis of Ig in the vessel wall(not immune complexes or Ig deposition from the bloodstream). Histologic exam of aorta sections showed mild vasculitis predominately affecting the adventitial layer, with many plasma cells in the inflammatory infiltrate. Immune fluorescence (IF) for Ig isotypes in aorta tissue sections showed cytoplasmic IF with large numbers of cells producing IgA and fewer producing IgM in the adventitial layer. No detectable IgG-producing cells were found by IF. Control aorta showed no IF for any isotype. Coronary artery sections from each of 4 other cases of fatal acute/subacute KS in which the vasculitis affected all 3 layers of the vessel wall revealed IgA-producing cells by immunohistochemistry in all three layers. Coronary artery sections from 2 children who died of non-KS illnesses revealed no IgA-producing cells. PCR analysis using primers specific for the leader sequences of the 6 families of heavy chain variable regions and a primer in the constant region of theα gene demonstrated that α transcripts expressed in the vascular cDNA library utilize gene segments of the VH1, VH3, VH4, and VH5 families. RT-PCR on control aorta mRNA using the same primers was negative for α transcripts. We conclude that there is a marked B-cell response within the vasculitic tissue in KS with unusual local IgA production in this non-lymphoid, non-mucosal tissue. We speculate that the observed IgA and IgM response without IgG relatively early in KS suggests an antigen-driven immune response to an etiologic agent with a respiratory or gastrointestinal portal of entry.