New Methods in Cardiovascular Biology Detection of Anti–1-AR Autoantibodies in Heart Failure by a Cell-Based Competition ELISA

Rationale: Autoantibodies directed against the second extracellular loop of the cardiac 1-adrenergic receptor (1-AR) are thought to contribute to the pathogenesis of dilated cardiomyopathy (DCM) and Chagas heart disease. Various approaches have been used to detect such autoantibodies; however, the reported prevalence varies largely, depending on the detection method used. Objective: We analyzed sera from 167 DCM patients (ejection fraction <45%) and from 110 age-matched volunteers who did not report any heart disease themselves, with an often used simple peptide-ELISA approach, and compared it with a novel whole cell–based ELISA, using cells expressing the full transgene for the human 1-AR. Additionally, 35 patients with hypertensive heart disease with preserved ejection fraction were investigated. Methods and Results: The novel assay was designed according to the currently most reliable anti-TSH receptor antibody-ELISA used to diagnose Graves disease (“third-generation assay”) and also detects the target antibodies by competition with a specific monoclonal anti–1-AR antibody (1-AR MAb) directed against the functionally relevant 1-AR epitope. Anti–1-AR antibodies were detected in 60 % of DCM patients and in 8 % of healthy volunteers using the same cutoff values. The prevalence of these antibodies was 17 % in patients with hypertensive heart disease. Anti–1-AR antibody titers (defined as inhibition of 1-AR MAb-binding) wer