Selective APRIL blockade delays systemic lupus erythematosus in mouse

Autor: Mahdia Benkhoucha, Marie-Laure Santiago-Raber, Céline Manzin-Lorenzi, Ngoc Lan Tran, Bertrand Huard
Rok vydání: 2012
Předmět:
Male
RNA
Messenger/genetics
lcsh:Medicine
ddc:616.07
Pathogenesis
Mice
0302 clinical medicine
Lupus Erythematosus
Systemic
lcsh:Science
Mice
Knockout
0303 health sciences
Multidisciplinary
Systemic lupus erythematosus
Mice
Inbred NZB
Antibodies
Monoclonal
Animal Models
Flow Cytometry
3. Good health
Lupus Erythematosus
Systemic/immunology/metabolism/prevention & control
Antibodies
Antinuclear
Medicine
Female
Tumor necrosis factor alpha
medicine.symptom
Spleen/immunology/metabolism/pathology
Research Article
Tumor Necrosis Factor-alpha/genetics/metabolism
Immunology
Tumor Necrosis Factor Ligand Superfamily Member 13
Blotting
Western
Inflammation
Biology
Real-Time Polymerase Chain Reaction
Autoimmune Diseases
03 medical and health sciences
Model Organisms
Immune system
Rheumatology
medicine
Animals
RNA
Messenger
Autoantibodies
030304 developmental biology
030203 arthritis & rheumatology
Antibodies
Antinuclear/blood
Lupus erythematosus
Tumor Necrosis Factor-alpha
lcsh:R
Autoantibody
medicine.disease
Antibodies
Monoclonal/pharmacology
Blockade
Mice
Inbred C57BL
Clinical Immunology
lcsh:Q
Autoantibodies/blood
Tumor Necrosis Factor Ligand Superfamily Member 13/antagonists & inhibitors/physiology
Spleen
Zdroj: PloS one
PLOS ONE, Vol. 7, No 2 (2012) P. e31837
PLoS ONE, Vol 7, Iss 2, p e31837 (2012)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0031837
Popis: 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.
Databáze: OpenAIRE
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