Serum perfluorooctane sulfonate and perfluorooctanoic acid concentrations and longitudinal systemic lupus outcomes

BACKGROUND: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are persistent per- and polyfluoroalkyl substances (PFAS) with immunomodulatory properties, but their role in systemic lupus erythematosus (SLE) outcomes remains unclear. We examined whether serum PFOS and PFOA concentrations were associated with subsequent increase in disease activity and damage accrual in SLE. METHODS: We studied patients from the McGill University Health Centre Lupus Registry. A random sub-cohort of 100 patients with physician-confirmed SLE was selected. Blood samples for measurements of 69 PFAS congeners were collected between July 1997 and January 2023 within an overall follow-up period from July 1997 to September 2025. PFOS and PFOA were the only congeners detected in >50% of samples. Outcomes were time to a ≥4-point increase in the SLE Disease Activity Index 2000 (SLEDAI-2K) and time to first increase in the Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) per interquartile range increase in PFOS and PFOA concentrations. RESULTS: During follow-up, 53 participants experienced a ≥4-point increase in SLEDAI-2K and 45 experienced an increase in SLICC-DI. Higher PFOS (HR = 1.15, 95% CI 1.01-1.31) and PFOA concentrations (HR = 1.29, 95% CI: 1.09-1.52) were associated with a greater hazard of a ≥4-point increase in SLEDAI-2K. Increased risk of damage accrual was also associated with PFOS (HR = 1.20, 95% CI 1.03-1.39). CONCLUSIONS: Higher serum PFOS concentrations were associated with increases in both SLE disease activity and damage accrual, whereas higher PFOA concentrations were associated with increased SLE disease activity.