OBJECTIVES: To assess the long-term risk of systemic lupus erythematosus (SLE) following antinuclear antibody (ANA) positivity in a nationwide cohort. METHODS: We followed ANA-tested, SLE-free individuals from 2000-2017 using national laboratory and health registers. ANA tests included ELISA-like connective tissue disease screening (ANA-CTD), single-dilution ANA (SDT-ANA) at dilution 1:160, and end point ANA titre (EPT-ANA) at dilutions 1:160-1:1280. In routine practice, ANA-CTD is often used in general practice, SDT-ANA and EPT-ANA in secondary and tertiary care. Hazard ratios (HR) of SLE were estimated using Cox models, and 5-year cumulative incidence using Kaplan-Meier methods. RESULTS: Among 342 777 ANA-tested individuals, 647 developed SLE. ANA positivity was strongly associated with SLE. ANA-CTD positivity conferred the highest risk (HR 67.3, 95% CI 45.8-99.0), followed by SDT-ANA (HR 18.0, 95% CI 14.4-22.5). Homogeneous and speckled SDT-ANA patterns carried the greatest risk (HR 15.7 and 7.90), with 5-year cumulative incidences up to 9.18% and 5.29% for strongly positive ANA intensity. Risk was highest within the first year, but remained elevated beyond five years for homogeneous and speckled patterns. Absolute risks were highest in younger individuals (18-30 years), reaching 5-year cumulative incidences of 4.99% for ANA-CTD, 4.12% for SDT-ANA, and 15.0% for EPT-ANA. CONCLUSIONS: ANA positivity was associated with markedly elevated short-term and sustained long-term SLE risk, particularly in younger adults and individuals with high-intensity homogeneous or speckled patterns. Nonetheless, absolute risk remained low, highlighting the need to interpret ANA results within a broader clinical context, and caution against direct extrapolation to unselected primary care populations.
Saint-Aubain et al. (2026) studied this question.