Exaggerated circulating Th-1 cytokine response in early rheumatoid arthritis patients with nodules.

BACKGROUND Immunohistochemical studies of the rheumatoid nodule (RN) suggest it is a Th1 granuloma, with focal vasculitis, yet the pathogenesis remains unclear and little is known about circulating cytokines in these patients. OBJECTIVE We studied circulating cytokines in DMARD-naïve RA patients to investigate associations with subcutaneous RN. METHODS 149 DMARD-naïve adults with early RA (symptom duration ≤ 2 years) were assessed using the Simplified Disease Activity Index (SDAI), and hand and feet radiographs were scored using the modified Larsen method. Circulating cytokines and growth factors representative of T-helper cell 1(Th1) and Th2 cell, macrophages, and fibroblasts were measured using the Bio-Plex® suspension array system. RESULTS Of 149 patients, 34 (22.8%) had subcutaneous RN, and these patients had more severe disease with higher mean swollen joint counts (p=0.02), SDAI (p=0.04) and modified Larsen scores (p=0.004). There were no differences in Rheumatoid Factor or anti-cyclic citrullinated peptide antibody positivity between patients with RN and those without RN. Patients with RN showed significantly higher levels of circulating IL-12 (p=0.02), IL-2 (p=0.048), and VEGF (p=0.033) levels, with a trend towards higher levels of IL-7 (p=0.056), IFN-γ (p=0.059) and IL-8 (p=0.074) compared to those without RN. CONCLUSIONS DMARD-naïve early RA patients with RN had more severe disease than those without RN, and showed an exaggerated circulating Th1 and macrophage cytokine profile.