ABSTRACT: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms. An infectious cause is likely, but specific antigenic targets have eluded 50 years of study. Peripheral blood plasmablasts become ~70% antigen-specific 1-2 weeks after antigen stimulation. We isolated single plasmablasts from children with KD and prepared 60 monoclonal antibodies (mAbs). Thirty-two mAbs recognize antigens localized to intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs recognize a specific peptide that blocks binding to the inclusion bodies. IgG antibody to the peptide epitope was identified in sera prior to therapy with intravenous gammaglobulin in 5/8 KD patients at day >8 after illness onset and 0/17 infant controls (p < 0.01). These results identify a specific protein epitope targeted by the antibody response to KD and will facilitate understanding pathogenesis and developing diagnostic assays for this important worldwide pediatric problem.

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