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

Abstract

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 62 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-c (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.