Extracellular HMGB1 induces several responses, including the elaboration of proinflammatory cytokines, cell proliferation and stromal cell matrix responses.10 Emerging evidence indicates that HMGB1 contributes to many diseases with dysregulated matrix responses such as rheumatoid arthritis (RA), liver fibrosis and progressive pulmonary fibrosis11 and HMGB1 binding and signalling through TLR4 mediate cytokine tissue injury. This evidence concerns the gene TLR4 and rheumatoid arthritis.