title: Autoantibodies Specifically Against β1 Adrenergic Receptors and Adverse Clinical Outcome in Patients With Chronic Systolic Heart Failure in the β-Blocker Era: The Importance of Immunoglobulin G3 Subclass.
abstract: OBJECTIVE
  To elucidate the prevalence and role of β1 adrenergic receptor autoantibodies (β1AR-AAb) belonging to the immunoglobulin (Ig)G3 subclass in patients with heart failure (HF) treated with β-adrenergic blockers.
  
  
  BACKGROUND
  Several cardiac AAbs have been reported to be present in sera from patients with dilated cardiomyopathy and other etiologies. Among AAbs, those recognizing β1AR-AAbs show agonist-like effects, have detrimental effects on cardiomyocytes, and may induce persistent myocardial damage.
  
  
  METHODS
  We quantify total IgG and IgG3 subclass β1AR-AAb in subjects with chronic stable HF with long-term follow-up.
  
  
  RESULTS
  In our study cohort of 121 subjects, non-IgG3-β1AR-AAb and IgG3-β1AR-AAb were found to be positive in 20 (17%) and 26 patients (21%), respectively. The positive rate of IgG3-β1AR-AAb was significantly higher for those with nonischemic compared with ischemic HF etiology (27% vs 8%, P = .01), but the positive rate for non-IgG3-β1AR-AAb was similar between the 2 groups (18% vs 16%, respectively, P = NS). There were no significant differences in clinical and echocardiographic measures among total β1AR-AAb negative, non-IgG3-β1AR-AAb positive, and IgG3-β1AR-AAb positive groups at baseline. During 2.2 ± 1.2 years of follow-up, we observed similar rates of the composite endpoint of all-cause mortality, cardiac transplantation, or hospitalization resulting from HF between total IgG-β1AR-AAb negative and positive patients. However, the composite endpoint events were significantly more common in the patients without than in those with IgG3-β1AR-AAb (P = .048, log-rank test).
  
  
  CONCLUSIONS
  Presence of IgG3-β1AR-AAb, not total IgG, was associated with paradoxically more favorable outcomes in our cohort of patients with chronic systolic HF largely treated by β-blockers.
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagatomo
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Daniel
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kirsop
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Alan
authors.initials: A
authors.lastname: Borowski
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH. Electronic address: tangw@ccf.org.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D054143:Heart Failure, Systolic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000097:blood / Q000276:immunology*; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1
keywords: Autoantibody; IgG3; β-blocker; β1-adrenergic receptor