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Scientific article
Open access
English

Selective APRIL blockade delays systemic lupus erythematosus in mouse

Published inPloS one, vol. 7, no. 2, e31837
Publication date2012
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.

Keywords
  • Animals
  • Antibodies, Antinuclear/blood
  • Antibodies, Monoclonal/pharmacology
  • Autoantibodies/blood
  • Blotting, Western
  • Female
  • Flow Cytometry
  • Lupus Erythematosus, Systemic/immunology/metabolism/prevention & control
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Mice, Knockout
  • RNA, Messenger/genetics
  • Real-Time Polymerase Chain Reaction
  • Spleen/immunology/metabolism/pathology
  • Tumor Necrosis Factor Ligand Superfamily Member 13/antagonists & inhibitors/physiology
  • Tumor Necrosis Factor-alpha/genetics/metabolism
Citation (ISO format)
HUARD, Bertrand et al. Selective APRIL blockade delays systemic lupus erythematosus in mouse. In: PloS one, 2012, vol. 7, n° 2, p. e31837. doi: 10.1371/journal.pone.0031837
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Article (Published version)
Identifiers
ISSN of the journal1932-6203
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244downloads

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