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The Journal of Immunology, 2005, 175: 8386-8391.
Copyright © 2005 by The American Association of Immunologists

Cloning the Arterial IgA Antibody Response during Acute Kawasaki Disease1

Anne H. Rowley2,*,{dagger}, Stanford T. Shulman*, Francesca L. Garcia*, Judith A. Guzman-Cottrill*, Masaru Miura*, Hannah L. Lee* and Susan C. Baker{ddagger}

Departments of * Pediatrics and {dagger} Microbiology/Immunology, The Feinberg School of Medicine, Northwestern University, The Children’s Memorial Hospital, Chicago, Illinois 60611; and {ddagger} Department of Microbiology/Immunology, Stritch School of Medicine, Loyola University, Maywood, IL 60153

Kawasaki disease (KD) is the most common acquired cardiac disease in children in developed nations. The etiology of KD is unknown but likely to be a ubiquitous microbial agent. Previously, we showed that oligoclonal IgA plasma cells infiltrate coronary arteries and other inflamed tissues in acute KD. We demonstrated that a synthetic Ab made using an {alpha} H chain sequence prevalent in acute KD arterial tissue detected Ag in acute KD coronary arteries, lung, and other inflamed tissues and that Ag localized to cytoplasmic inclusion bodies in the acute KD ciliated bronchial epithelium. In this study, we synthesized a panel of mAbs from {alpha} and {kappa} chain sequences present in the KD arterial wall and tested the Abs for binding to acute KD tissues. We report that all of the synthetic mAbs that bind to acute KD tissues detect Ag in cytoplasmic inclusion bodies in the acute KD ciliated bronchial epithelium. Abs made from {alpha} sequences that were prevalent in KD arterial tissue show stronger binding to acute KD tissues than Abs made from less prevalent sequences. These findings highlight the likely importance of the inclusion bodies in the etiopathogenesis of acute KD, confirm that the IgA Ab response in acute KD is Ag driven, and demonstrate the usefulness of cloning the Ab response in diseased tissues to identify disease-relevant Ags.







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