A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease

Anne H. Rowley, Susan C. Baker, David Arrollo, Leah J. Gruen, Tetyana Bodnar, Nancy Innocentini, Matthew Hackbart, Yazmin E. Cruz-Pulido, Kristine M. Wylie, Kwang Youn A. Kim, Stanford T. Shulman

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

BACKGROUND: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1-2 weeks after infection. METHODS: We isolated single peripheral blood plasmablasts from children with KD 1-3 weeks after onset and prepared 60 monoclonal antibodies (mAbs). We used the mAbs to identify their target antigens and assessed serologic response among KD patients and controls to specific antigen. RESULTS: Thirty-two mAbs from 9 of 11 patients recognize antigen within intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of fatal cases. Five of these mAbs, from 3 patients with coronary aneurysms, recognize a specific peptide, which blocks binding to inclusion bodies. Sera from 5/8 KD patients day ≥ 8 after illness onset, compared with 0/17 infant controls (P < .01), recognized the KD peptide antigen. CONCLUSIONS: These results identify a protein epitope targeted by the antibody response to KD and provide a means to elucidate the pathogenesis of this important worldwide pediatric problem.

Original languageEnglish (US)
Pages (from-to)158-168
Number of pages11
JournalThe Journal of infectious diseases
Volume222
Issue number1
DOIs
StatePublished - Jun 16 2020

Keywords

  • Kawasaki disease
  • monoclonal antibodies
  • plasmablast

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Rowley, A. H., Baker, S. C., Arrollo, D., Gruen, L. J., Bodnar, T., Innocentini, N., Hackbart, M., Cruz-Pulido, Y. E., Wylie, K. M., Kim, K. Y. A., & Shulman, S. T. (2020). A Protein Epitope Targeted by the Antibody Response to Kawasaki Disease. The Journal of infectious diseases, 222(1), 158-168. https://doi.org/10.1093/infdis/jiaa066