B lymphocytes and lupus nephritis: new insights into pathogenesis and targeted therapies

Lupus nephritis (LN) in systemic lupus erythematosus (SLE) remains a major cause of morbidity and end-stage renal disease. While therapies such as corticosteroids, cyclophosphamide, and mycophenolate mofetil have improved outcomes, a significant proportion of patients have refractory disease or are unable to tolerate these agents. Limitations in existing therapies, along with advances in our understanding of the immunopathogenesis of SLE, have resulted in the development of new immunosuppressive and immunomodulatory treatments for SLE/LN. Dysfunction of the B lymphocyte-an important component of adaptive immunity-is thought to be important in the pathogenesis of SLE/LN. The goal of this study is to review our current understanding of the role of B cells in the pathogenesis of SLE, and to discuss new and emerging therapies that selectively target B cells in patients with SLE/LN. Novel strategies discussed include B-cell depletion by the monoclonal antibodies to B-cell markers, rituximab and epratuzumab; 'pharmapheresis' of pathogenic antibodies to dsDNA, by abetimus; blockade of T-cell costimulation of B cells by abatacept, belatacept, BG9588, and IDEC-131; and blockade of B-cell stimulation by belimumab. Preliminary results are promising, but in the absence of large controlled trials, caution must be exercised prior to the widespread use and acceptance of these treatments.