Immunol Res. 2026 Aug 10;74(1):83. doi: 10.1007/s12026-026-09818-7.
ABSTRACT
Anti-topoisomerase I (anti-Scl-70) antibodies are strongly associated with systemic sclerosis and fibrotic organ involvement. However, their significance in ANA-positive individuals without established systemic sclerosis remains unclear. We investigated whether isolated anti-Scl-70 positivity is associated with subclinical cardiac involvement. This retrospective single-center study included 486 ANA-positive individuals identified between 2016 and 2026. Patients were classified as anti-Scl-70-positive (n = 242) or anti-Scl-70-negative (n = 244). Individuals with systemic sclerosis, other rheumatologic diseases, cardiovascular disease (except hypertension), malignancy, or advanced renal/hepatic disease were excluded. All anti-Scl-70-positive patients remained free of systemic sclerosis during at least 12 months of follow-up. Electrocardiographic Diastolic Index-1 (EDI-1) and EDI-2 were calculated from standard 12-lead ECGs. Demographic characteristics, inflammatory markers, ANA titers, and most ENA antibodies were similar between groups. Anti-Ro52 positivity was more frequent in anti-Scl-70-positive individuals (p = 0.004). EDI-1 was significantly lower, whereas EDI-2 was significantly higher in the anti-Scl-70-positive group (both p < 0.001). Among patients with available echocardiographic data, anti-Scl-70-positive individuals demonstrated higher E/e' ratios (p = 0.004) and lower LV-GLS values (p = 0.046). EDI-1 showed a strong correlation with E/e' (rs = -0.898, p < 0.001). In multivariable analysis, anti-Scl-70 positivity was the only independent predictor of electrocardiographic diastolic dysfunction (p < 0.001). Isolated anti-Scl-70 positivity is associated with impaired electrocardiographic markers of diastolic function in ANA-positive individuals without overt systemic sclerosis. These findings suggest that isolated anti-Scl-70 positivity is associated with early subclinical myocardial involvement and support further investigation of ECG-derived diastolic indices as potential screening tools in this population.
PMID:42572046 | DOI:10.1007/s12026-026-09818-7