Novel approaches in the treatment of lupus nephritis

Lupus nephritis can be managed successfully in the majority of cases; most therapies, however, are associated with significant side-effects. Several n ew agents aiming at specific stages in the pathogenesis of lupus are in dif ferent phases of clinical trials. The central role of lymphocytes makes the m targets of various therapeutic approaches. Lymphocyte depletion can be ac hieved by high-dose chemotherapy with or without bone marrow transplantatio n. Nucleoside analogs selectively deplete mononuclear cells; antibodies aga inst T or B cell surface antigens target specific subsets of lymphocytes. S ynchronized plasmapheresis has been used in an attempt to delete pathogenic lymphocyte clones activated by plasmapheresis. Treating patients with DNas e or neutralizing pathogenic antibodies by administering specific binding p eptides or inducing specific anti-idiotype antibodies may prevent immune co mplex formation and/or deposition. Blocking the complement cascade or some of the inflammatory mediators like thromboxane A(2) may be efficacious even if immune complex deposition could not be prevented. Inducing antigen-spec ific tolerance or interfering with important interactions between T-lymphoc ytes and other cells by blocking CD40 ligand or decreasing the level of int erleukin-10 are some of the other approaches currently under clinical inves tigation.