Beta-1 adrenergic receptor autoantibody (anti-β1-AR autoantibody) (β1-AAB)

Pathogenic anti-beta-1 adrenergic receptor (β1-AR) autoantibodies are functional immunoglobulins, primarily of the IgG class, that specifically bind to the second extracellular loop (ECL2) of the β1-AR (Jahns et al., 2004). These autoantibodies act as persistent agonists, mimicking the effects of natural catecholamines but failing to induce the typical receptor desensitization and internalization that normally follows activation (Wallukat & Schimke, 2014). This chronic activation leads to sustained cyclic AMP (cAMP) production and calcium overload in cardiomyocytes, resulting in myocyte apoptosis, cardiac remodeling, and the development of dilated cardiomyopathy (DCM) and heart failure (Bornholz et al., 2014). These antibodies are found in a significant proportion of patients with idiopathic DCM and are considered a key driver of disease progression (Müller et al., 2014). Therapeutic strategies focus on the removal of these antibodies via immunoadsorption or their neutralization using specific DNA aptamers like BC 007, which binds to the autoantibody and prevents its interaction with the receptor (Haberland et al., 2016). Unlike standard beta-blockers that target the receptor itself, these emerging therapies aim to eliminate the pathological stimulus provided by the autoantibodies.

Other names

Anti-beta-1 adrenergic receptor autoantibodyβ1-AR autoantibodyAnti-β1-AR ECL2 antibodyAgonistic β1-adrenergic receptor autoantibodyBeta-1-adrenoceptor autoantibody

Neutralization of circulating autoantibodies to prevent chronic agonistic stimulation of the beta-1 adrenergic receptor.