[Progress and perspectives in the treatment of systemic lupus erythematosus]

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women in childbearing age. SLE tissue damage is mediated by autoantibodies, complement activation and immune complexes deposition. The disease is diagnosed on the basis of its clinical manifestations and the demonstration of characteristic immunological phenomena, especially antinuclear antibodies. Management of the disease includes regular monitoring of disease activity, avoidance of predisposing factors and therapy guided by the activity and severity of the leading organ manifestation. Treatment ranges from nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents. Corticosteroids form the basis of all regimens. Antimalarials and azathioprine are important for treating mild and moderate SLE cases, especially for the long time. Cyclophosphamide given intravenously is the current gold standard for severe lupus nephritis. More recently new strategies for immunosuppression in SLE, that interfere with the syntesis of DNA and nucleotides have been developed (such as mycophenolate mofetil, fludarabine and cladribine). Other agents like cyclosporine and tacrolimus inhibit effect of the activation signals for T cells by inhibition of calcineurin. Some monoclonal antibodies against cytokines or components of the complement system interfere with the effector phase of the immune response. Abetimus (LJP-394) inhibits the production of anti-dsDNA antibodies and may prevent glomerulonephritis caused by anti-DNA containing immune complexes. Somatic gene therapy is also a novel approach in autoimmune disorders and my be a valuable method of SLE therapy in the future. The adrenal steroid prasterone (DHEA) has also shown benefitial effects in mild to moderate SLE. Finally, autologous stem cell transplantation can induce tolerance to self-antigens and cause significant improvement in SLE patients. However, new therapeutic strategies must be tested according to the established principles of clinical trial methods.