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

Abstract

Anti-beta-1-adrenergic receptor antibodies (anti-b 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 b 1 AR to promote pathological cardiac remodelling and b 1 AR desensitization and downregulation. The prevalence of anti-b 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-b 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-b 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-b 1 AR Abs and highlight the opportunity for further research and development in this area.--

A standardised FACS assay based on native, receptor transfected cells for the clinical diagnosis and monitoring of β1-adrenergic receptor autoantibodies in human heart disease

“…By this method 70% of a cohort of end-stage DCM-patients was judged autoantibodypositive. This value fits well with the prevalence of circulating β 1 AR-autoantibodies previously assessed via their capability to stimulate the receptor, which was 50%-70% in DCM patients vs. only 5%-10% in the healthy population [2,8,11,14]. In summary, the proposed analytical procedure appears suitable for discriminating physiological and pathological levels of β 1 AR-autoantibodies in human IgG preparations.…”

“…Novel therapy-modalities specifically directed against cardio-noxious β 1 AR-autoantibodies comprise extracorporeal IgG-absorption [14][15][16] and neutralisation/clearance of β 1 AR-autoantibodies by systemic administration of synthetic epitope mimics [17][18][19][20]. DCM patients with reduced cardiac function are considered to benefit from therapies selective for β 1 AR-autoantibodies only when they are positive for β 1 AR-autoantibodies [14,15].…”

“…DCM patients with reduced cardiac function are considered to benefit from therapies selective for β 1 AR-autoantibodies only when they are positive for β 1 AR-autoantibodies [14,15]. Therefore, implementation of therapies specifically targeting β 1 AR-autoantibodies requires a companion diagnostic that enables (i) the selection of autoantibody-positive patients, and (ii) the monitoring of autoantibody levels during therapy (response assessment) and follow-up (indication for re-treatment).…”

Autoantibody profiling on a plasmonic nano-gold chip for the early detection of hypertensive heart disease

“…Our results are consistent with the prior experimental studies from Matsui et al (6) and Wallukat et al (7), suggesting a role of anti-β1 adrenergic antibodies in the development of ventricular hypertrophy. Novel therapies targeting the anti-beta-1-adrenergic receptor antibodies could also offer an opportunity for future research and development in this area (27).…”

The relationship between β1‐adrenergic and M2‐muscarinic receptor autoantibodies and hypertrophic cardiomyopathy

“…During the past two decades, research has begun to illuminate the immune mechanisms that underlie HF (Luft, 2013;Patel, & Hernandez, 2013;Xia, & Kellems, 2011). Autoantibodies that bind to G-protein-coupled receptors of the neuroendocrine system play a causal role in the pathogenesis of cardiovascular diseases.…”