title: Selective APRIL blockade delays systemic lupus erythematosus in mouse.
abstract: SLE pathogenesis is complex, but it is now widely accepted that autoantibodies play a key role in the process by forming excessive immune complexes; their deposits within tissues leading to inflammation and functional damages. A proliferation inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) superfamily mediating antibody-producing plasma cell (PC)-survival that may be involved in the duration of pathogenic autoantibodies in lupus. We found significant increases of APRIL at the mRNA and protein levels in bone marrow but not spleen cells from NZB/W lupus mice, as compared to control mice. Selective antibody-mediated APRIL blockade delays disease development in this model by preventing proteinuria, kidney lesions, and mortality. Notably, this was achieved by decreasing anti-DNA and anti-chromatin autoantibody levels, without any perturbation of B- and T-cell homeostasis. Thus, anti-APRIL treatment may constitute an alternative therapy in SLE highly specific to PCs compared to other B-cell targeting therapies tested in this disease, and likely to be associated with less adverse effects than any anti-inflammatory and immunosuppressant agents previously used.
authors.affiliation: Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Huard
authors.forename: Ngoc Lan
authors.initials: NL
authors.lastname: Tran
authors.forename: Mahdia
authors.initials: M
authors.lastname: Benkhoucha
authors.forename: Céline
authors.initials: C
authors.lastname: Manzin-Lorenzi
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Santiago-Raber
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001323:Autoantibodies / Q000097:blood; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D012333:RNA, Messenger; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha