The association of plasma IL-1Ra and related cytokines with radiographic severity of early knee osteoarthritis

OBJECTIVE: We aimed to evaluate the association between inflammatory biomarkers in peripheral blood and severity of knee osteoarthritis (OA). METHODS: We performed a cross-sectional study in participants with frequent knee pain, evaluated radiographic and clinical severity. We measured inflammatory biomarkers: plasma (p) IL-1Ra, IL-1β, IL-18, serum (s) CD14, hsCRP and bone and cartilage biomarkers: urine (u) CTX-II, (s) HA, COMP, CTX-I, PIIANP. We assessed radiographic severity by Kellgren-Lawrence (KL) grading and Osteoarthritis Research Society International (OARSI) standardized scoring atlas; and clinical severity by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: 139 participants (82% women, mean ± SD age: 55.5 ± 7.8 years) were included. (p) IL-1Ra was negatively associated with radiographic severity by KL grading (Spearman rho = −0.197, P = 0.021), osteophytes (Spearman rho = −0.217, P = 0.011), and joint space narrowing of index knee (Spearman rho = −0.172, P = 0.045); and KL sum score of both knees (Spearman rho = −0.180, P = 0.035), after adjustment for age, gender and body mass index (BMI). Other inflammatory markers were not associated with radiographic severity. Cartilage degradation markers (u) CTXII and (s) COMP were modestly associated with radiographic severity after adjustment. In multivariate models, (s) hsCRP and the bone and cartilage biomarkers, but not the inflammatory biomarkers, were associated with radiographic severity. CONCLUSION: Among the inflammatory biomarkers in peripheral blood, IL-1Ra was negatively associated with radiographic severity in this early knee OA cohort.