Targeting anti-beta-1-adrenergic receptor antibodies for dilated cardiomyopathy

Anti-beta-1-adrenergic receptor antibodies (anti-(1)AR Abs) have long been implicated in the pathogenesis of dilated cardiomyopathy (DCM). It is believed that these autoantibodies bind to and constitutively stimulate the (1)AR to promote pathological cardiac remodelling and (1)AR desensitization and downregulation. The prevalence of anti-(1)AR Abs in patients with DCM ranges from 26 to 60, and the presence of these autoantibodies correlates with a poor prognosis. Several small studies have shown improvements in functional status, haemodynamics, and biomarkers of heart failure upon removal or neutralization of these antibodies from the sera of affected patients. Traditionally, removal of anti-(1)AR Abs required immunoadsorption therapy with apheresis columns directed against human immunoglobulins (Igs) and subsequent i.v. Ig infusion, thereby essentially performing a plasma exchange transfusion. However, recent advances have allowed the development of small peptides and nucleotide sequences that specifically target and neutralize anti-(1)AR Abs, providing a hopeful avenue for future drug development to treat DCM. Herein, we briefly review the clinical literature of therapy directed against anti-(1)AR Abs and highlight the opportunity for further research and development in this area.