title: B Cell-Activating Factor (BAFF)-Targeted B Cell Therapies in Inflammatory Bowel Diseases.
abstract: Inflammatory bowel diseases (IBD) involve dysregulated immune responses to gut antigens in genetically predisposed individuals. While a better elucidation of IBD pathophysiology has considerably increased the number of treatment options, the need for more effective therapeutic strategies remains a pressing priority. Defects of both non-hematopoietic (epithelial and stromal) and hematopoietic (lymphoid and myeloid) cells have been described in patients with IBD. Within the lymphoid system, alterations of the T cell compartment are viewed as essential in the pathogenesis of IBD. However, growing evidence points to the additional perturbations of the B cell compartment. Indeed, the intestinal lamina propria from IBD patients shows an increased presence of antibody-secreting plasma cells, which correlates with enhanced pro-inflammatory immunoglobulin G production and changes in the quality of non-inflammatory IgA responses. These B cell abnormalities are compounded by the emergence of systemic antibody responses to various autologous and microbial antigens, which predates the clinical diagnosis of IBD and identifies patients with complicated disease. It is presently unclear whether such antibody responses play a pathogenetic role, as B cell depletion with the CD20-targeting monoclonal antibody rituximab did not ameliorate ulcerative colitis in a clinical trial. However, it must be noted that unresponsiveness to rituximab is also observed also in some patients with autoimmune disorders usually responsive to B cell-depleting therapies. In this review, we discussed mechanistic aspects of B cell-based therapies and their potential role in IBD with a special interest on BAFF and BAFF-targeting therapies buoyed by the success of anti-BAFF treatments in rheumatologic disorders.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. mathieuuzzan@gmail.com.|The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. mathieuuzzan@gmail.com.
authors.forename: Mathieu
authors.identifier: 0000-0002-7761-2879
authors.initials: M
authors.lastname: Uzzan
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.|Departments of Medicine and Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
authors.affiliation: Department of Gastroenterology, Beaujon Hospital, APHP, Denis Diderot University, Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Treton
authors.affiliation: Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.|The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Mehandru
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D053301:B-Cell Maturation Antigen / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D058990:Molecular Targeted Therapy; D009000:Monocytes / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D053303:Transmembrane Activator and CAML Interactor Protein; D000069283:Rituximab; C511911:belimumab; C524618:TACI receptor-IgG Fc fragment fusion protein; C575974:tabalumab
keywords: B cells; BAFF; Inflammatory bowel diseases