Cytokines (IL-15, IL-21, and IFN-gamma) in rheumatoid arthritis: association with positivity to autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) and clinical activity

摘要

Introduction Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-gamma have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-gamma with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity. Methodology This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-gamma, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI). Results The serum levels of IL-15, IL-21, and IFN-gamma, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices. Conclusions Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-gamma are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity.