In addition, HMGB1 in its reduced form binds to CXCL12 via the chemokine receptor CXCR4 in rheumatoid arthritis (RA), and a high concentration of CXCL12/HMGB1 hybrid complex is dependent on the JAK/STAT pathway to maintain the inflammatory response.70 This evidence concerns the gene CXCL12 and rheumatoid arthritis.