Abstract
We reported the unique finding that IgA plasma cells are prominent in the inflammatory infiltrate in the vascular wall in acute fatal Kawasaki Disease (KD). Additionally, we sequenced IgA heavy chain genes in vascular tissue from three fatal acute KD cases and found evidence of an oligoclonal IgA response in all three KD patients, indicating an antigen-driven process. The presence of oligoclonal IgA-producing cells in the KD vascular wall provides a unique opportunity to identify the specific antigens being targeted by synthesizing the corresponding oligoclonal antibodies in vitro. Recent advances in molecular immunology enable the cloning of specific immunoglobulin heavy and light chain variable region genes into mammalian immunoglobulin expression vectors for the production of specific antibodies in tissue culture. We have prepared four synthetic KD antibodies from oligoclonal IgA genes prevalent in the KD vascular wall. In preliminary experiments, one of the synthetic antibodies binds to tissue sections from the spleen of a child who died of KD on day 13 of illness, but not to control spleen sections. This synthetic KD antibody also binds to upper respiratory tract sections from two other fatal KD cases, but not to control respiratory tract. Identification of the targeted antigen is underway by Western blot and cDNA library screening analysis. The use of synthetic KD antibodies provides a new approach for identifying antigens important in KD pathogenesis, as well for identification of the etiologic agent of KD and the development of a diagnostic test.
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Rowley, A., Baker, S., Garcia, F. et al. Identification of Kawasaki Disease (KD) Antigens Using Synthetic KD Antibodies. Pediatr Res 53, 160 (2003). https://doi.org/10.1203/00006450-200301000-00039
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DOI: https://doi.org/10.1203/00006450-200301000-00039
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