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Objectives 1) To investigate whether fluctuations in anti-double stranded DNA immunoglobulin G (anti-dsDNA IgG) antibodies and C3 levels predict clinical flares and sustained activity in patients with serologically active clinically quiescent (SACQ) systemic lupus erythematosus (SLE), and 2) to explore additional risk factors for flare.Methods SLE patient data from the University College London Hospital Lupus cohort were collected (2020–2025), and SACQ cases were identified. SACQ was defined as at least 6 months of abnormal anti-dsDNA IgG 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 with generalized estimating equations (GEE). Kaplan–Meier curves estimated time to flare.Results Sixty patients (531 visits) were included. Over a mean 3.3-year follow-up, 38 patients (63.3%) developed at least 1 flare. Figure 1 illustrates the dynamic transitions of the cohort across disease states. No baseline characteristics were associated with flare onset, except for follow-up duration (p = 0.005). Higher anti-dsDNA IgG and C3 independently predicted flare (OR 1.04, 95% CI 1.01–1.08; OR 0.79, 95% CI 0.70–0.90, respectively), and sustained activity (OR 1.08, 95% CI 1.04–1.13; OR 0.81, 95% 0.73–0.89), including moderate-to-severe flares (OR 1.07, 95% CI 1.03–1.12; OR 0.73, 95% CI 0.59–0.90) and disease-activity (OR 1.08, 95% CI 1.04–1.13; OR 0.63 (0.53–0.75). This association persisted after adjusting for therapeutic changes, as shown in table 1 and 2. Higher categories of anti-dsDNA IgG antibody increase (none, slight, moderate) were associated with earlier flare occurrence (log-rank p = 0.002). Hydroxychloroquine (HCQ) tapering or discontinuation invariably preceded moderate-to-severe (perfect prediction).Abstract PO:12:313 Figure and TablesConclusions Most SACQ patients developed clinical flares, indicating that persistent serological activity is rarely benign. Higher anti-dsDNA IgG antibody levels and lower C3 concentrations at the preceding visit independently predict disease activity, supporting close monitoring despite prolonged clinical quiescence. Maintenance of HCQ appears protective against relevant activity.