HMGB1 and rheumatoid arthritis: The specific conformational changes induced in CXCR4 by the heterocomplex (21), the prevention of CXCL12 degradation when the chemokine is complexed with HMGB1 (59), the various signaling cascades triggered by the heterocomplex in active RA, all need consideration when novel therapeutic strategies for chronic inflammatory diseases will be exploited.