Targeting anti-beta-1-adrenergic receptor antibodies for dilated cardiomyopathy. 2013

Priyesh A Patel, and Adrian F Hernandez
Duke Clinical Research Institute, Durham, NC, USA. patel.priyesha@gmail.com

Anti-beta-1-adrenergic receptor antibodies (anti-β1AR Abs) have long been implicated in the pathogenesis of dilated cardiomyopathy (DCM). It is believed that these autoantibodies bind to and constitutively stimulate the β1AR to promote pathological cardiac remodelling and β1AR desensitization and downregulation. The prevalence of anti-β1AR 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-β1AR 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-β1AR Abs, providing a hopeful avenue for future drug development to treat DCM. Herein, we briefly review the clinical literature of therapy directed against anti-β1AR Abs and highlight the opportunity for further research and development in this area.

UI MeSH Term Description Entries
D002311 Cardiomyopathy, Dilated A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein. Cardiomyopathy, Congestive,Congestive Cardiomyopathy,Dilated Cardiomyopathy,Cardiomyopathy, Dilated, 1a,Cardiomyopathy, Dilated, Autosomal Recessive,Cardiomyopathy, Dilated, CMD1A,Cardiomyopathy, Dilated, LMNA,Cardiomyopathy, Dilated, With Conduction Defect 1,Cardiomyopathy, Dilated, with Conduction Deffect1,Cardiomyopathy, Familial Idiopathic,Cardiomyopathy, Idiopathic Dilated,Cardiomyopathies, Congestive,Cardiomyopathies, Dilated,Cardiomyopathies, Familial Idiopathic,Cardiomyopathies, Idiopathic Dilated,Congestive Cardiomyopathies,Dilated Cardiomyopathies,Dilated Cardiomyopathies, Idiopathic,Dilated Cardiomyopathy, Idiopathic,Familial Idiopathic Cardiomyopathies,Familial Idiopathic Cardiomyopathy,Idiopathic Cardiomyopathies, Familial,Idiopathic Cardiomyopathy, Familial,Idiopathic Dilated Cardiomyopathies,Idiopathic Dilated Cardiomyopathy
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D015551 Autoimmunity Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES. Autoimmune Response,Autoimmune Responses,Autoimmunities
D018342 Receptors, Adrenergic, beta-1 A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems. Adrenergic beta-1 Receptor,Adrenergic beta-1 Receptors,Receptors, beta-1 Adrenergic,beta-1 Adrenergic Receptors,Adrenergic Receptor, beta-1,Receptor, Adrenergic, beta-1,beta 1 Adrenergic Receptor,Adrenergic Receptor, beta 1,Adrenergic Receptors, beta-1,Adrenergic beta 1 Receptor,Adrenergic beta 1 Receptors,Receptor, Adrenergic beta-1,Receptor, beta-1 Adrenergic,Receptors, Adrenergic beta-1,Receptors, beta 1 Adrenergic,beta 1 Adrenergic Receptors,beta-1 Adrenergic Receptor,beta-1 Receptor, Adrenergic,beta-1 Receptors, Adrenergic

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