Neutralizing autoantibodies against interferon alpha in systemic lupus erythematosus: Prevalence, age of onset, and clinical associations

Objective Type I interferons (IFN) drive systemic lupus erythematosus (SLE) pathogenesis. Some patients develop neutralizing IFN autoantibodies (anti-IFN ab), which theoretically could modify disease activity. We aimed to determine the prevalence of anti-IFN ab in patients with SLE, identify the age and when during the disease course of anti-IFN ab emerge, and assess their association with organ damage. Methods This cross-sectional study included 173 SLE patients from the Lund Lupus Cohort. Samples taken at routine outpatient visits were analyzed for anti-IFN ab using ELISA, and positive samples were tested for IFN neutralizing capacity with a gene-reporter assay. Longitudinal samples were analyzed to determine the time-point and age of first positive sample. Demographic and clinical data were obtained from research registries. Results Eighteen (10.4%) patients were positive for anti-IFN ab by ELISA. Among these, antibodies from nine patients (5.2%) displayed IFN neutralizing capacity. No statistically significant differences were detected between patients positive for neutralizing antibodies and antibody-negative patients with respect to demography, organ damage or ACR classification criteria. The group with neutralizing antibodies were slightly older (median age 59 vs 45 years, p = .14) and had a higher proportion of renal involvement (67% vs 33%, p = .088). Longitudinal analysis of samples from patients with neutralizing anti-IFN ab revealed two age-related patterns: late-onset (≥65 years, n = 4), including one patient positive at diagnosis at age 69, and early-onset (≤40 years, n = 5), with antibodies present at or soon after diagnosis in four cases. Organ damage did not differ between patients with or without neutralizing antibodies (p = .65). At the latest follow-up (2–38 years after anti-IFN ab detection), three of nine patients remained free of organ damage. Conclusions Approximately 5% of SLE patients have neutralizing anti-IFN antibodies, which may present early in disease or develop later in life. While late-onset antibodies may reflect age-related changes in immune regulation and early-onset antibodies could potentially modulate IFN-driven mechanisms, our data do not support a protective effect against organ damage.