Novel approaches in the treatment of lupus nephritis

In systemic lupus erythematosus hyperactive helper T-cells drive polyclonal B-cell activation and secretion of pathogenic auto-antibodies. The autoant ibodies form immune complexes with their respective auto-antigens, which in turn deposit in sites such as the kidney and initiate a destructive inflam matory reaction. Lupus nephritis can be managed successfully in the majorit y of cases; however, the most widely used immunosuppressive therapies, nota bly corticosteroids and cyclophosphamide are non-specific and are associate d with substantial toxicities. Novel treatments for lupus nephritis have to be at least as effective and less toxic than existing therapies. The ultim ate aim is to develop treatments that target specific steps in the disease process. Novel therapeutic strategies in the short-term more likely will fo cus on refining regimens of drugs that are already in use (mycophenolate mo fetil, adenosine analogues) and combinations of existing chemotherapeutic a gents, as well as attempts to achieve immunological reconstitution using im munoablative chemotherapy with or without haematopoietic stem cell rescue. Several new agents targeting specific steps in the pathogenesis of lupus ar e in various phases of clinical development. Interrupting the interactions between T-lymphocytes and other cells by blocking co-stimulatory molecules, such as CD40 ligand or CTLA4-Ig, may interfere with the early steps of pat hogenesis. Blocking IL-10 may decrease auto-antibody production and help no rmalise T-cell function. Treating patients with DNase or interfering with t he complement cascade by blocking C5, or neutralising pathogenic antibodies by administering specific binding peptides or inducing specific anti-idiot ype antibodies may prevent immune complex formation and/or deposition.