The documented involvement of RAGE and/or HMGB1 in various autoimmune disorders, such as MG [9], systemic lupus erythematosus [48], [49], polymyositis [50], rheumatoid arthritis [51], [52] in conjunction with the new findings of these molecules in different cells in specific areas of thymus involved in positive (self MHC restriction) and/or negative selection (elimination of autoreactive T cells), namely thymic epithelial cells, raises the possibility of disturbances in central tolerance mechanisms linked to the RAGE axis. The gene discussed is HMGB1; the disease is rheumatoid arthritis.