Circulating anti-Ro/Sjögren's syndrome-related antigen A antibodies and risk of heart rate-corrected QT interval prolongation: a meta-analysis.

Authors

Pietro Enea Lazzerini, Mark Markovich Melamud, Evgeny Alexandrovich Ermakov, Vadim Vyacheslavovich Konkov, Valentina Nikolaevna Buneva, Riccardo Accioli, Alessandra Cartocci, Anna Cantore, Viola Salvini, Decoroso Verrengia, Maurizio Acampa, Pier Leopoldo Capecchi, Mohamed Boutjdir

Published in

European heart journal open. Volume 6. Issue 5. Pages oeag123. Epub Aug 14, 2026.

Abstract

Accumulating evidence indicates that anti-Ro/Sjögren's syndrome-related antigen A (SSA) antibodies, specifically the anti-Ro/SSA-52kD subtype, can promote heart rate-corrected QT interval (QTc) prolongation by inhibiting the hERG-K⁺ channel. However, the numerous clinical studies published over the past two decades yielded conflicting results. This meta-analysis aims at pooling the available data to provide clarity on this clinically relevant issue.
A systematic review was performed for clinical studies comparing QTc in anti-Ro/SSA-positive vs. -negative subjects. Standardized mean differences (SMDs) and odds ratios (ORs) were compared using random effects models. The risk of bias was assessed using RoBANS2, Egger's test and contour-enhanced funnel plots. Twenty-five studies were included, pooling 2122 anti-Ro/SSA-positive and 8865 anti-Ro/SSA-negative subjects. Overall, anti-Ro/SSA-positivity is associated with a longer QTc [SMD = 0.36 (0.18-0.53), P < 0.001], and a more than two times higher risk of QTc prolongation [OR = 2.24 (1.54-3.27), P < 0.001]. Several sub-analyses supported and refined these findings. Specifically, in anti-Ro/SSA-positive patients with unselected connective tissue disease, QTc absolute values are higher [SMD = 0.56 (0.20-0.93), P = 0.0026] and QTc prolongation occurs more frequently [OR = 6.99 (2.35-20.75), P < 0.001] than in negative patients; furthermore, QTc prolongation is also more common in systemic lupus erythematosus patients with circulating anti-Ro/SSA-antibodies than in those without [OR = 1.86 (1.19-2.90), P = 0.006]. Finally, in anti-Ro/SSA-52kD-positive subjects, the QTc is longer compared to the negative ones [SMD = 0.43 (0.15-0.71), P = 0.002].
This meta-analysis supports the conclusion that circulating anti-Ro/SSA-antibodies per se represents a significant risk factor for QTc prolongation. However, the presence of several conflicting studies suggests that a more accurate investigation of specific factors, such as the impact of individual antibody subtype levels (anti-52kD/anti-60kD), will be critical to fully clarify the topic and its implications in clinical practice.

PMID:
42877758
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.

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