It is widely accepted that maternal anti-Ro/SSA antibodies are associated with congenital heart block.1 Meanwhile, the potential role of autoantibodies in adult conduction system abnormalities remains underexplored. Isolated cases have reported reversible atrioventricular block (AVB) in adult patients with positive anti-Ro/SSA antibodies, with the hypothesis that conduction delays result from reversible calcium current inhibition.2 Additionally, observational studies have identified anti-Ro/SSA positivity as an independent risk factor for conduction system disturbances in adult patients, even after adjusting for concurrent autoimmune disease.3,4
For the first time in 2026, a consensus statement from the European Society of Cardiology recommended considering testing for anti-Ro/SSA antibodies in “exceptional cases of unexplained or progressive conduction disease.”5 However, the proportion of patients with high-grade AVB that may be related to autoantibodies remains unknown, and prior observational studies have been limited by sample size. Villuendas et al evaluated 3586 patients with pacemakers placed at <50 years of age for idiopathic AVB and noted only 20 in which anti-Ro/SSA was specifically tested.6 Notably, within those tested, 80% exhibited positivity. For those in whom immunosuppression was attempted, 50% demonstrated improvement.6
Simultaneously, anti-Ro/SSA antibodies are common in the general population.7 The clinical significance of positive antinuclear antibodies (ANA) without a diagnosis of autoimmune disease remains poorly understood. However, observational studies suggest that positive ANA is associated with increased rates of cardiovascular events and mortality, even after adjusting for cardiovascular risk factors such as age, sex, hypertension, smoking, diabetes, body mass index, renal function, statin use, and hyperlipidemia.8
We hypothesize that anti-Ro/SSA antibodies may be independently associated with treatable and reversible conduction abnormalities in adult patients diagnosed with idiopathic high-grade AVB, both with and without preexisting autoimmune disease. Testing this idea would first require a better understanding of the prevalence of anti-Ro/SSA positivity through larger datasets of patients who receive lab testing upon presentation. While economically more challenging, testing should ideally be conducted through immune western blotting for optimal sensitivity and specificity.9 The role of anti-Ro/SSA antibodies should be explored through multivariate logistic regression after controlling for other risk factors of conduction system disease, such as age, known autoimmune disease, myocarditis, coronary artery disease, dilated cardiomyopathy, and metabolic disorders.10 Ultimately, exploring the impact of autoantibodies on adult conduction system abnormalities would expand our understanding of the clinical implications of positive serologies, which are frequently thought to be benign, and potentially recategorize idiopathic cases and expand targeted therapies for complete heart block.
DISCLOSURE STATEMENT
The authors report no funding or conflicts of interest. The opinions and assertions expressed are those of the authors and do not reflect the official policy or position of the Uniformed Services University of the Health Sciences, Walter Reed National Military Medical Center, or the Department of War.
References
- 1.Chameides L, Truex RC, Vetter V, Rashkind WJ, Galioto FM Jr, Noonan JA.. Association of maternal systemic lupus erythematosus with congenital complete heart block. N Engl J Med. 1977;297(22):1204–1207. doi: 10.1056/NEJM197712012972203. [DOI] [PubMed] [Google Scholar]
- 2.Santos-Pardo I, Martínez-Morillo M, Villuendas R, Bayes-Genis A.. Anti-Ro antibodies and reversible atrioventricular block. N Engl J Med. 2013;368(24):2335–2337. doi: 10.1056/NEJMc1300484. [DOI] [PubMed] [Google Scholar]
- 3.Hua C, Jiang C, Wang Z, et al. Association between anti-SSA autoantibodies and conduction disturbances in heart failure. Heart Rhythm. 2024;21(12):2583–2590. doi: 10.1016/j.hrthm.2024.05.060. [DOI] [PubMed] [Google Scholar]
- 4.Akuka A, Ben-Shabat N, Watad A, et al. Association of anti-Ro seropositivity with cardiac rhythm and conduction disturbances. Eur Heart J. 2022;43(47):4912–4919. doi: 10.1093/eurheartj/ehac516. [DOI] [PubMed] [Google Scholar]
- 5.Finocchiaro G, Zorzi A, Abela M, et al. Abnormal electrocardiogram findings in athletes. Eur Heart J. 2026;47(2):152–169. doi: 10.1093/eurheartj/ehaf646. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Villuendas R, Olivé A, Juncà G, et al. Autoimmunity and atrioventricular block of unknown etiology in adults: the role of anti-Ro/SSA antibodies. J Am Coll Cardiol. 2014;63(13):1335–1336. doi: 10.1016/j.jacc.2013.10.086. [DOI] [PubMed] [Google Scholar]
- 7.Cao R, Lv H, Tang B, Lu Y.. Anti-Ro/SSA antibodies in adult arrhythmias: pathogenesis, clinical implications, and therapeutic strategies. Front Immunol. 2025;16:1561061. doi: 10.3389/fimmu.2025.1561061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Solow EB, Vongpatanasin W, Skaug B, Karp DR, Ayers C, de Lemos JA.. Antinuclear antibodies are associated with all-cause mortality and cardiovascular outcomes in the general population. J Am Coll Cardiol. 2015;65(24):2669–2670. doi: 10.1016/j.jacc.2015.03.578. [DOI] [PubMed] [Google Scholar]
- 9.Lazzerini P, Capecchi P, Boutjdir M.. Anti-Ro/SSA-antibody testing for isolated atrioventricular block in adults: a diagnostic and therapeutic work-up. Eur Heart J. 2026;47(23):2917–2921. doi: 10.1093/eurheartj/ehag177. [DOI] [PubMed] [Google Scholar]
- 10.Balla C, Canovi L, Zuin M, et al. Cardiac conduction disorders due to acquired or genetic causes in young adults: a review of the current literature. J Am Heart Assoc. 2025;14(9):e040274. doi: 10.1161/JAHA.124.040274. [DOI] [PMC free article] [PubMed] [Google Scholar]