Association between inflammatory cytokines and immune–checkpoint molecule in rheumatoid arthritis

Background Anti-citrullinated peptide antibodies (ACPA) and inflammatory cytokines play important roles in the development of rheumatoid arthritis (RA). T cell immunoglobulin and mucin–domain containing–3 (TIM–3) is an immune-checkpoint molecule involved in inhibitory signaling. Galectin–9 (Gal–9) mediated ligation of TIM–3 induces the amelioration of autoimmune diseases. TIM–3 is expressed in synovial osteoclasts and involved in the rheumatoid bone destruction. The aim of this study was to investigate the relationships between inflammatory cytokines and immune–checkpoint molecules in RA patients. Methods Serum levels of interleukin–6 (IL–6), tumor necrosis factor–α (TNF–α), soluble TIM–3 (sTIM–3) and Gal–9 were determined by ELISA. Patients were stratified into two groups based on ACPA titers: low-medium ACPA (ACPA Results Elevated serum levels of inflammatory cytokines were correlated with DAS28–ESR in RA patients. Although serum levels of sTIM–3 were elevated in RA patients, significant correlations between sTIM–3 and cytokines (IL–6 or TNF–α) were observed exclusively in RA patients with low-medium ACPA titers (Conclusions Our data indicated that there are positive correlations between circulating inflammatory cytokines and checkpoint molecules in RA patients and these interactions can be modulated by ACPA status or joint damage stage