Autoimmune antibodies in arrhythmia: a narrative review of potential therapeutic targets to prevent overtreatment.

BACKGROUND AND OBJECTIVE

The global prevalence of autoimmune diseases (ADs) has increased significantly in recent decades, with cardiovascular complications such as arrhythmia being a major cause of mortality. Traditional mechanistic explanations cannot account for all cases, and autoimmune antibodies have emerged as a novel pathogenic factor. This review summarizes the associations between autoimmune antibodies and arrhythmias, outlining the molecular mechanisms by which these antibodies interfere with cardiac ion channels, receptors, and cellular structures, and providing new insights into the diagnosis and treatment of AD-related arrhythmias.

METHODS

Recent studies on autoimmune antibodies and atrial/ventricular arrhythmias or cardiac conduction system damage were retrieved from academic databases (PubMed, Embase, Cochrane Library, and Web of Science), particularly those focusing on antibody types, target sites, and electrophysiological changes. The literature screening process included study type (case-control and animal experiments) and publication date (January 1980 to January 2025), but not language (any language was permitted).

KEY CONTENT AND FINDINGS

(I) In atrial arrhythmias, anti-myosin heavy chain antibodies directly damage cardiomyocytes, with a 60% positivity rate in patients with idiopathic paroxysmal atrial fibrillation (AF). Anti-Kir3.4 antibodies shorten the atrial effective refractory period (AERP) by binding to the channel's extracellular domain, increasing susceptibility to AF by 2.8-fold. Anti-β1-R and anti-M2-R antibodies promote atrial fibrosis, elevating the risk of AF. (II) In cardiac conduction system damage, anti-Ro/Sjögren's syndrome A (SSA) antibodies cross the placenta to damage fetal cardiac conduction tissue, causing congenital heart block (CHB) with a recurrence risk of 12-25%. In adults, the presence of anti-Ro/SSA antibodies is associated with atrioventricular block (AVB) and prolonged QT interval, possibly via inhibition of L-type calcium channels (LCCs). (III) In ventricular arrhythmias, anti-β1-R antibodies enhance LCCs and reduce potassium currents (IK1 and Ito), prolonging the QT interval and inducing ventricular tachycardia (VT). These antibodies are independent risk factors in dilated cardiomyopathy (DCM). Anti-calcium channel antibodies interfere with LCCs, promoting VT and sudden cardiac death (SCD), particularly in patients without structural heart disease. (IV) Regarding therapeutic strategies, hydroxychloroquine during pregnancy reduces the risk of CHB recurrence. In adults, glucocorticoids and hydroxychloroquine may obviate the need for pacemaker implantation for some cases of AVB.

CONCLUSIONS

Autoimmune antibodies regulate cardiac electrophysiology and structural remodeling through multiple pathways, serving as key pathogenic mechanisms for arrhythmias. Further research into the molecular details of antibody-ion channel interactions and the clinical translation of targeted immunotherapies are needed to improve arrhythmia outcomes in patients with AD.