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International Immunology Advance Access originally published online on February 1, 2008
International Immunology 2008 20(3):445-452; doi:10.1093/intimm/dxn004
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Thomas B. Martins1, James L. Hoffman2, Nancy H. Augustine1,2, Amit R. Phansalkar1, Vincent A. Fischetti3, John B. Zabriskie3,4, Patrick P. Cleary5, James M. Musser6, L. George Veasy2 and Harry R. Hill1,2

1 Associated Regional and University Pathologists Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA
2 Department of Pathology, Pediatrics and Medicine, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 84108, USA
3 Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, NY, USA
4 Research Division, Hospital for Special Surgery, Rockefeller University, New York, NY, USA
5 Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN, USA
6 Center for Molecular and Translational Human Infectious Diseases Research, Methodist Hospital Research Institute, Houston, TX, USA

Correspondence to: H. R. Hill; E-mail: harry.hill{at}path.utah.edu

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.

Keywords: acute rheumatic fever, antibody responses, cross-reactivity, group A streptococcus, molecular mimicry, multiplexed immunoassay, rheumatic heart disease

Transmitting editor: M. C. Nussenzweig

Received 22 February 2007, accepted 5 January 2008.


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