Title: B Cell Modulation Strategies in Autoimmunity: The SLE Example
Volume: 17
Issue: 29
Author(s): M. Manuela Rosado, Andrea Picchianti Diamanti, Federica Capolunghi and Rita Carsetti
Affiliation:
Keywords:
B cells, Autoantibodies, Biologic drugs, SLE, autoimmune disorders, immune-suppression, germinal centers, prostaglandins, inflammation, chronic lymphocytic leukaemia (CLL)
Abstract: The paradigm that T cells are the prime effectors of autoimmune diseases has been recently challenged by growing evidence that B-lymphocytes play a role in the development, re-activation and persistence of autoimmune disorders. B-cells of different subsets may play different roles in autoimmune pathologies due to their ability to secrete antibodies, produce cytokines, present antigen and form ectopic germinal centers. Thus, a given therapeutic approach or drug may have distinct outcomes depending on which specific B cell subset is targeted.
Immunosuppressive therapies such as azathioprine (AZA), cyclophosphamide (CyC) or methotrexate (MTX) are conventionally used in autoimmune diseases with the aim of reducing disease activity and improving the patient's general health conditions. These treatments do not target a specific cellular type or subset and have substantial side effects, such as impairment of liver function and fertility. Moreover, autoimmune patients may be refractory to immunosuppressive therapy. In these cases finding an effective treatment becomes a challenge. The fast evolution in antibody technology is leading to the production of a wide array of humanized monoclonal antibodies, targeting specific cell types or pathways, initiating a new era in the treatment of autoimmune disorders. In addition, the recent discovery that toll like receptors (TLRs) activation can fire up autoimmunity in humans and maintain disease gives the grounds for the development of new drugs targeting the TLR/MyD88 pathway. In contrast to conventional immune-suppression, the availability of drugs interfering with Bcell specific pathogenetic pathways gives the possibility to choose therapies tailored to each disease and, possibly, to each patient.