Comprehensive analysis of antibody responses to streptococcal and tissue antigens in patients with acute rheumatic fever

Thomas B. Martins, James I. Hoffman, Nancy H. Augustine, Amit R. Phansalkar, Vincent A. Fischetti, John B. Zabriskie, Patrick P. Cleary, James M. Musser, L. George Veasy, Harry R. Hill

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Acute rheumatic fever (ARF) is an autoimmune disease occurring in individuals following untreated group A streptococcal infection believed to be triggered by antibodies to bacterial components that cross-react with human tissues. We developed a multiplexed immunoassay for the simultaneous quantitation of antibodies to nine streptococcal-related antigens including streptolysin O (SLO), DNase B, collagen I and IV, fibronectin, myosin, group A carbohydrate, M6 protein and streptococcal C5a peptidase. Utilizing this method, we examined serum from 49 ARF, 58 pharyngitis patients and age- and sex-matched controls in samples collected at initial disease onset, and at 4 weeks, 6 months and 1 year after diagnosis. Antibody responses were significantly higher for SLO, DNase B, M6 protein, group A carbohydrate and the cross-reactive antigens collagen I and myosin in ARF compared with pharyngitis patients (P ≤ 0.05). Moreover, we found significantly elevated antibody responses in the ARF patients with rheumatic heart disease to fibronectin and collagen I compared with ARF patients without heart disease. The major differences between the ARF patients with and without carditis appear to be in the immune response to the putative heart valve components, collagen I and fibronectin.

Original languageEnglish (US)
Pages (from-to)445-452
Number of pages8
JournalInternational Immunology
Volume20
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • Acute rheumatic fever
  • Antibody responses
  • Cross-reactivity
  • Group A streptococcus
  • Molecular mimicry
  • Multiplexed immunoassay
  • Rheumatic heart disease

ASJC Scopus subject areas

  • Immunology

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