Immunoadsorption therapy for dilated cardiomyopathy and pulmonary arterial hypertension

Abstract

Dilated cardiomyopathy (DCM) which is a common cause of heart failure is often related to elevated levels of autoantibodies (AABs) against cardiac structural or functional proteins. Among several AABs which react against cardiac cellular proteins that have been detected in sera from DCM patients, those against β(1)-adreno-receptors (β(1)-ARs) appeared particularly relevant from a pathophysiological point of view. During the last 15 years several studies evaluating the short-term efficacy of immunoadsorption (IA) in idiopathic DCM have shown improvement in cardiac function and patient outcome. However, the invasive and complicated aspects of the IA, which is also costly, have limited its broad clinical application as long as only its short-term efficacy has been definitely proved. Autoimmunity is also suspected to play a key role in the pathogenesis of pulmonary arterial hypertension (PAH). Recently we identified functional AABs against the α(1)-AR and/or the endothelin-A-receptor (ETA) in sera of patients with PAH. These AABs activate the receptors like corresponding agonists but, unlike the agonists, the AABs induce long-lasting stimulatory effects and do not desensitize the receptors. The AABs against the α(1)-AR and the ETA-receptor belong to IgG3 and IGg2 subclass, respectively, and can be removed by IA. The first 5 potential transplant candidates with idiopathic PAH who underwent IA showed good results after this therapy. This update aims to summarize the present knowledge about the role of AABs in the etiopathogenesis of DCM and PAH and the potential therapeutic benefits of AAB removal by IA. Special attention is focused on the therapeutic benefits of IA for patients with life-threatening end-stage disease where all pharmacological therapeutic options are exhausted.