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435 ANALYSIS OF ANTIBODY RESPONSES IN PATIENTS WITH ACUTE RHEUMATIC FEVER EMPLOYING A MULTI-PLEXED FLUORESCENT IMMUNOASSAY
  1. J. L. Hoffman,
  2. T. B. Martins,
  3. N. H. Augustine,
  4. L. G. Veasy,
  5. J. M. Musser,
  6. H. R. Hill
  1. Departments of Pediatrics, Pathology and Internal Medicine, University of Utah School of Medicine

Abstract

Purpose Acute rheumatic fever (ARF) remains a major problem worldwide. We have seen over 600 cases of ARF in the past 15 years (NEJM 316:421-427, 1987, J. Peds. 124:9-15 1994, Ped. 113:168-172, 2004). The specific pathogenesis of ARF and especially rheumatic heart disease (RHD) remains unknown. Previous studies have suggested molecular mimicry between components of strains of the group A streptococcus (GAS) and human tissue resulting in an immune response directed at these tissues.

Methods We employed a multiplexed fluorescent microsphere system to develop an assay requiring only 5 μl of serum to simultaneously assess the serum concentration of two non-specific streptococcal antibodies (anti-streptolysin O (ASO), anti-DNase B) and four antibodies specific to human tissues (myosin, collagen I, collagen IV, and fibronectin).

Results We found significantly higher antibody activity in the ARF patients (n=20) to nonspecific streptococcal enzymes ASO and DNase B compared to pharyngitis patients (n=10) (ASO: 2519 mean fluorescent intensity vs. 1412 MFI p=0.005, anti-DNase B: 4795 MFI vs. 2268 MFI p=0.0006). We also found significant increases in antibody to collagen I, a component of heart valves, collagen IV, a component of basement membrane in several tissues, and fibronectin (anti-collagen I: 277 MFI vs. 136 MFI p=0.029, anti-collagen IV: 200 MFI vs. 50 MFI p=0.005, anti-fibronectin 1279 MFI vs. 1169 MFI p=0.007). In contrast, we did not see significantly elevated antibody to myosin which is associated with myocarditis (anti-myosin 649 MFI vs. 310 MFI p=0.069). In 10 patients with ARF with carditis vs. 10 patients with ARF without carditis, we found significantly higher levels of ASO, anti-DNase B, and anti-myosin (ASO: 2968 MFI vs. 2071 MFI p=0.035, anti-DNase B: 6037 MFI vs. 3554 MFI p=0.015, anti-myosin: 1037 MFI vs. 262 MFI p=0.019).

Conclusion Employing this system, we have shown that ARF patients are hyper-responsive to all of these antigens, and carditis patients have a higher response to specific antigens than non-carditis patients. Such data derived from this multi-analyte system, may allow us to dissect the critical role of this molecular mimicry in the pathogenesis of acute rheumatic fever and rheumatic heart disease.

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