Anti-Ro/SSA Antibodies and the Autoimmune Long-QT Syndrome.

Pietro Enea Lazzerini,Mohamed Boutjdir,Franco Laghi-Pasini,Pier Leopoldo Capecchi

doi:10.3389/fmed.2021.730161

Abstract

Autoimmunity is increasingly recognized as a novel pathogenic mechanism for cardiac arrhythmias. Several arrhythmogenic autoantibodies have been identified, cross-reacting with different types of surface proteins critically involved in the cardiomyocyte electrophysiology, primarily ion channels (autoimmune cardiac channelopathies). Specifically, some of these autoantibodies can prolong the action potential duration leading to acquired long-QT syndrome (LQTS), a condition known to increase the risk of life-threatening ventricular arrhythmias, particularly Torsades de Pointes (TdP). The most investigated form of autoimmune LQTS is associated with the presence of circulating anti-Ro/SSA-antibodies, frequently found in patients with autoimmune diseases (AD), but also in a significant proportion of apparently healthy subjects of the general population. Accumulating evidence indicates that anti-Ro/SSA-antibodies can markedly delay the ventricular repolarization via a direct inhibitory cross-reaction with the extracellular pore region of the human-ether-a-go-go-related (hERG) potassium channel, resulting in a higher propensity for anti-Ro/SSA-positive subjects to develop LQTS and ventricular arrhythmias/TdP. Recent population data demonstrate that the risk of LQTS in subjects with circulating anti-Ro/SSA antibodies is significantly increased independent of a history of overt AD, intriguingly suggesting that these autoantibodies may silently contribute to a number of cases of ventricular arrhythmias and cardiac arrest in the general population. In this review, we highlight the current knowledge in this topic providing complementary basic, clinical and population health perspectives.

Highlights

The long QT-syndrome (LQTS) is a cardiac electric disorder characterized by an abnormal prolongation of the heart rate-corrected QT interval (QTc) on the electrocardiogram [1] which predisposes to life-threatening ventricular arrhythmias (VAs), Torsades de Pointes (TdP) [1,2,3]
By analyzing a prospective cohort of 25 TdP subjects consecutively collected from the general population, we found the presence of anti-Ro/SSA-52kD-antibodies in over 50% of patients, in most cases without a history of autoimmune diseases (AD) [24]
Mounting evidence from clinical and experimental studies indicates that anti-Ro/SSA-antibodies can markedly affect the ventricular repolarization via a direct inhibitory cross-reaction with the extracellular pore region of the cardiac human ether-à-go-go related gene K+ channel (hERG-K+)channel, resulting in an increased predisposition to LQTS/TdP in anti-Ro/SSA-positive patients

Summary

Introduction

The long QT-syndrome (LQTS) is a cardiac electric disorder characterized by an abnormal prolongation of the heart rate-corrected QT interval (QTc) on the electrocardiogram (traditionally >440 ms; currently, >470 ms for men, and >480 ms for women) [1] which predisposes to life-threatening ventricular arrhythmias (VAs), Torsades de Pointes (TdP) [1,2,3]. Sham et al [68] reported that mean QTc was longer in SLE subjects with, rather than without circulating anti-Ro/SSA-antibodies, while Mostafavi et al [71] and Perez-Garcia et al [69] found that anti-Ro/SSA-antibodies were more commonly detectable and at a higher concentration when SLE patients with QTc prolongation were compared to those with a normal QTc. in a study using machine learning in 299 patients with SLE, Hu et al [72] identified antiRo/SSA positivity as one of the most important independent variables associated with QTc prolongation > 450 ms in these subjects.

Results

Conclusion