Prolonged serologically active clinically quiescent systemic lupus erythematosus: a longitudinal study on the role of IgG anti-dsDNA and C3.

Abstract

To assess whether fluctuations in Immunoglobulin G anti-double stranded DNA (IgG anti-dsDNA) antibodies and C3 levels predict flares and sustained activity in patients with prolonged serologically active clinically quiescent (SACQ) systemic lupus erythematosus (SLE), and to explore additional risk factors for flare. SLE patient data from the University College London Hospital Lupus cohort were collected (2020-2025). Prolonged SACQ was defined as ≥ 6 months of elevated IgG anti-dsDNA and/or low C3 without clinical activity (BILAG-2004 index D/E in all domains). Associations between biomarker changes and outcomes, adjusted for main confounders, were tested longitudinally with generalized estimating equations (GEE). Sixty patients (531 visits) were included. Over a mean 3.3-year follow-up, 38 patients (63.3%) experienced≥1 flare. Baseline characteristics were comparable between patients with and without flares, except for longer follow-up duration (p = 0.005) and a higher prevalence of anti-Ro positivity (p = 0.018) among those who developed flares. . In GEE-models, higher IgG anti-dsDNA and lower C3 levels independently predicted flares and sustained activity at the subsequent visit, including moderate-to-severe cases. Most SACQ patients developed clinical flares. Changes in IgG anti-dsDNA and C3 levels emerged as strong predictors of flare in prolonged SACQ patients in a visit-by-visit analysis, supporting close clinical monitoring and highlighting the value of serological trends despite the presence of prolonged clinical quiescence and sustained biomarker abnormalities.