Novel approaches in the treatment of lupus nephritis

Abstract

Lupus nephritis can be managed successfully in the majority of cases; most therapies, however, are associated with significant side-effects. Several new agents aiming at specific stages in the pathogenesis of lupus are in different phases of clinical trials. The central role of lymphocytes makes them targets of various therapeutic approaches. Lymphocyte depletion can be achieved by high-dose chemotherapy with or without bone marrow transplantation. Nucleoside analogs selectively deplete mononuclear cells; antibodies against T or B cell surface antigens target specific subsets of lymphocytes. Synchronized plasmapheresis has been used in an attempt to delete pathogenic lymphocyte clones activated by plasmapheresis. Treating patients with DNase or neutralizing pathogenic antibodies by administering specific binding peptides or inducing specific anti-idiotype antibodies may prevent immune complex formation and/or deposition. Blocking the complement cascade or some of the inflammatory mediators like thromboxane A₂ may be efficacious even if immune complex deposition could not be prevented. Inducing antigen-specific tolerance or interfering with important interactions between T-lymphocytes and other cells by blocking CD40 ligand or decreasing the level of interleukin-10 are some of the other approaches currently under clinical investigation.