title: Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE.
abstract: New insights into the mechanisms of autoimmune diseases have been obtained not only from preclinical studies, but also from clinical trials of pan-B-cell-directed therapy. Overall, the results of these clinical trials suggest that more-specific approaches focusing on pathogenic B-cell functions, and perhaps sparing or even enhancing regulatory B-cell activity, might be attractive alternatives. Importantly, pathogenic B-cell subpopulations function within a network of cellular interactions, many of which might require additional interventions to restore immunologic balance and suppress autoimmune disease. Thus, approaches that simultaneously target innate immune cells as well as multiple nodes of T-cell and B-cell interactions might hold the promise of improved therapeutic efficacy. Interfering with B-cell intracellular signalling pathways, altering their intracellular metabolic pathways and perturbing transcription factors are additional options. This Review critically analyses these approaches, examines the role of cytokines and other functions of B-lineage cells separate from antibody secretion, and provides insights into the potential next generation of therapies targeting B-lineage cells.
authors.affiliation: Departments of Medicine, Rheumatology and Clinical Immunology, Charité-University Medicine Berlin and the German Rheumatism Research Centre (DRFZ), Chariteplatz 01, Berlin 10117, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
authors.affiliation: RILITE Foundation, 1001 Research Park Boulevard, Suite 301, Charlottesville, Virginia 22911, USA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology; D053264:B-Cell Activating Factor / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology; D019317:Evidence-Based Medicine; D006801:Humans; D047589:Leukocyte Reduction Procedures / Q000379:methods; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D053264:B-Cell Activating Factor; D016207:Cytokines