Autoimmune disease. A problem of defective apoptosis.

Human autoimmune diseases share the common feature of an imbalance between the production and destruction of various cell types including lymphocytes (SLE), synovial cells (RA), and fibroblasts (scleroderma). Patients with SLE have increased levels of soluble Fas that inhibit proper apoptosis of lymphocytes. In animal models of autoimmune diseases, mutations of genes involved in apoptosis including Fas, Fas ligand, and the hematopoietic cell phosphatase gene have been identified. Oncogenes, including bcl-2, p53, and myc, that regulate apoptosis are also expressed abnormally. Potent inducers of apoptosis including steroids, azathioprine, cyclophosphamide, and methotrexate are the most efficacious therapies for autoimmune disease currently known. Specific therapies that induce apoptosis without incurring side effects should improve treatment of autoimmune disease.