HMGB1 synovial protein expression before and during infliximab therapy as detected by immunohistochemistry. Nuclear, cytoplasmic and extracellular HMGB1 protein expression is evident in the RA synovia in the lining layer as well as in cellular infiltrates and endothelium. (a) Moderate aberrant synovial HMGB1 expression before the start of infliximab therapy from patient number 5. (b) The second biopsy in patient number 5 taken during infliximab treatment showing increased extranuclear HMGB1 staining. (c) A marked endothelial expression of HMGB1 is evident before infliximab therapy in synovitis obtained from patient number 7. (d) Infliximab therapy for nine weeks resulted in reduced endothelial HMGB1 expression in patient number 7. Original magnification ×250 for (a) and (b), ×100 for (c) and (d).