Abstract 14424: Association of Beta-1 Adrenergic Receptor Autoantibodies With Heart Failure Risk in Systemic Sclerosis

Abstract

Introduction: Systemic sclerosis (SSc) is associated with the greatest independent risk of heart failure (HF) among systemic autoimmune diseases. Cardiac involvement in SSc also includes cardiomyopathy (CM), diastolic dysfunction (DD), and arrhythmias. Diffuse cutaneous SSc (dcSSc) is associated with greater cardiac risk than limited cutaneous SSc (lcSSc). Prior studies have examined the pathogenic roles of anti-beta-1 adrenergic receptor autoantibodies (β1AR-AAbs) and the protective role of the IgG3 subclass of β1AR-AAbs in HF. We aimed to investigate the associations between β1AR-AAb IgG/IgG3 seropositivity and disease phenotype in an SSc cohort. Methods: Serum samples were collected with informed consent from SSc patients with and without cardiac involvement, as approved by the Cleveland Clinic Institutional Review Board. Enzyme-linked immunosorbent assays were performed to investigate the presence of circulating IgG and IgG3 subtype β1AR-AAbs. Average optical density (OD) was compared between SSc and healthy control samples to establish seropositivity at the 2x control threshold level. Proportions of patients positive for β1AR-AAbs in different groups were compared using Fisher’s exact test. Results: Samples were collected from 36 SSc patients, of whom 20 (56%) had lcSSc and 15 (42%) had dcSSc. Cardiac involvement included HF, CM, DD, and arrhythmia, at least one of which was documented in 9 patients (25%). Of the total SSc cohort, 11 (31%) and 7 (19%) were positive for anti-β1AR IgG and IgG3 respectively. Between SSc patients with and without cardiac involvement, there was no significant difference in IgG or IgG3 positivity. There was a significant increase in IgG3 positivity in the lcSSc group compared to the dcSSc group at the 2x control threshold (p = 0.0125). Conclusions: High anti-β1AR IgG3 positivity is associated with less severe disease category (lcSSc vs. dcSSc) in our SSc cohort, supporting prior evidence of the protective role of the IgG3 subtype. A larger sample size will allow for further investigation of the associations between IgG/IgG3 β1AR-AAbs and cardiac involvement in SSc.