Considerable evidence exists implicating extracellular HMGB1 in the pathogenesis of a variety of autoimmune diseases. Anti-HMGB1 antibodies are present in the serum of patients with rheumatoid arthritis and drug-induced systemic lupus erythematosus (85, 86) . Furthermore, HMGB1 has been found to be overexpressed in the extracellular milieu of synovial biopsy specimens in rheumatoid and experimental arthritis (87, 88) . When given via direct intraarticular injection, HMGB1 induces arthritis in mice, while treatment with HMGB1 antagonists ameliorates collagen-induced arthritis in both rats and mice (89, 90) . Increased extracellular HMGB1 also is detectable in the dermis and epidermis of skin lesions in patients with cutaneous lupus erythematosus and in biopsy specimens of the minor salivary glands of patients with Sjogren's Syndrome (91, 92) .