title: Are autoantibodies the targets of B-cell-directed therapy?
abstract: B-cell-directed therapy-the use of agents that eliminate B cells or block cytokines important for B-cell function-is emerging as a promising approach to the treatment of rheumatic disease. Target diseases, including systemic lupus erythematosus (SLE), display diverse patterns of autoantibody production and aberrant activation of B cells. Despite the success of this general approach, the mechanisms by which B-cell-directed therapy ameliorates disease, and the role of autoantibodies as biomarkers of clinical response remain unclear. Importantly, although B-cell-directed therapy can reduce the production of some autoantibodies, the effects can be variable and heterogeneous, probably reflecting the critical (but ill-defined) roles of different B-cell and plasma cell populations in autoantibody production. Future studies during clinical trials of these agents are needed to define which B-cell and autoantibody populations are affected (or ought to be), and to discover informative biomarkers of clinical response that can be used to advance this therapeutic approach.
authors.affiliation: Department of Medicine and Immunology, Medical Research Service, Durham VA Hospital, NC 27705, USA. piset001@mc.duke.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Pisetsky
authors.forename: Amrie C
authors.initials: AC
authors.lastname: Grammer
authors.forename: Tony C
authors.initials: TC
authors.lastname: Ning
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001323:Autoantibodies / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D047589:Leukocyte Reduction Procedures; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008775:Methylprednisolone / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D008775:Methylprednisolone