title: The BAFF/APRIL system in SLE pathogenesis.
abstract: Systemic lupus erythematosus (SLE) is characterized by multisystem immune-mediated injury in the setting of autoimmunity to nuclear antigens. The clinical heterogeneity of SLE, the absence of universally agreed clinical trial end points, and the paucity of validated therapeutic targets have, historically, contributed to a lack of novel treatments for SLE. However, in 2011, a therapeutic monoclonal antibody that neutralizes the cytokine TNF ligand superfamily member 13B (also known as B-cell-activating factor of the TNF family [BAFF]), belimumab, became the first targeted therapy for SLE to have efficacy in a randomized clinical trial. Because of its specificity, the efficacy of belimumab provides an opportunity to increase understanding of SLE pathophysiology. Although belimumab depletes B cells, this effect is not as powerful as that of other B-cell-directed therapies that have not been proven efficacious in randomized clinical trials. In this article, therefore, we review results suggesting that neutralizing BAFF can have effects on the immune system other than depletion of B cells. We also identify aspects of the BAFF system for which data in relation to SLE are still missing, and we suggest studies to investigate the pathogenesis of SLE and ways to refine anti-BAFF therapies. The role of a related cytokine, TNF ligand superfamily member 13 (also known as a proliferation-inducing ligand [APRIL]) in SLE is much less well understood, and hence this review focuses on BAFF.
authors.affiliation: Department of Immunology, Monash University, Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Vic 3004, Australia.
authors.forename: Fabien B
authors.initials: FB
authors.lastname: Vincent
authors.affiliation: Monash University Centre for Inflammatory Diseases, Southern Clinical School, Monash Medical Centre, 246 Clayton Road, Clayton, Vic 3168, Australia.
authors.forename: Eric F
authors.initials: EF
authors.lastname: Morand
authors.affiliation: Department of Biochemistry, University of Lausanne, Boveresses 155, 1066 Epalinges, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Department of Immunology, Monash University, Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), 89 Commercial Road, Melbourne, Vic 3004, Australia.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015551:Autoimmunity; D053264:B-Cell Activating Factor / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000502:physiology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D007166:Immunosuppressive Agents; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C511911:belimumab