B cell targeted therapy in autoimmunity

Autoimmunity results from a break in self-tolerance involving humoral and/or cell-mediated immune mechanisms. Part of the pathological consequence of a failure in central and/or peripheral tolerance, results from survival and activation of seif-reactive B cells. Such B cells produce tissue-damaging pathogenic autoantibodies, and subsequent formation of complement-fixing immune complexes that contribute to tissue damage. Current pharmacological strategies for treating autoimmune diseases involve global use of broad-acting immunosuppressants that with long term use have associated toxicities. The present drive in drug development is towards therapies that target a specific biological pathway or pathogenic cell population. This review focuses on some of the emerging therapies based on co-stimulation blockers, and compounds which contribute to a specific B cells depletion, based on studies in animal models and human clinical studies. (C) 2007 Elsevier Ltd. All rights reserved.