Abstract 17040: Cardiac Autoantibody Production Defines Unique Heart Failure Phenotypes
Introduction: Autoimmunity is thought to play an important role in the pathogenesis of myocarditis and dilated cardiomyopathy. However, immunologic testing has not been effective in clearly differentiating autoimmune from other etiologies of heart failure (HF). We hypothesized that fluid-phase radioimmunoassays, which are widely used in screening programs for other organ-specific autoimmune diseases, might identify clinically relevant autoantibodies (Ab) in HF patients.
Methods: We developed immunoassays for Ab based on in vitro translation of cDNAs encoding human cardiac myosin and troponin followed by immunoprecipitation with patient sera in 96-well filtration plates. Study subjects (174 with HF and 74 controls) underwent comprehensive evaluation and testing for Ab and HLA-DQ/DR haplotype. HF etiology was assigned by investigators blinded to autoimmune test results. Primary analysis compared specific Ab according to HF etiology.
Results: Mean age was 48 yrs, 61% were male, and mean EF was 30% in HF patients. Anti-troponin Ab were detected more often in myocarditis and idiopathic dilated cardiomyopathy compared to other HF etiologies (20% vs. 5%, p=0.004); none were found in controls. In HF patients, anti-myosin Ab were more common than anti-troponin Ab (29% vs. 10%, p<0.0001) and were particularly enriched in myocarditis subjects vs. other causes of HF (p=0.007). Ab detection was not associated with age, EF or HLA genotype. Interestingly there was little overlap between anti-myosin and anti-troponin Ab production, with 87% of Ab-positive subjects having only a single Ab type detected.
Conclusions: Cardiac autoantibodies are relatively common in HF; however, their antigenic specificity varies with etiology. Troponin Ab are more specific to both myocarditis and idiopathic dilated cardiomyopathy. Differential Ab detection may be a marker or mediator of clinical risk in a subset of inflammatory cardiomyopathies.
- © 2010 by American Heart Association, Inc.