HLA-DR15-specific inhibition attenuates autoreactivity to the Goodpasture antigen.
Animals
Anti-Glomerular Basement Membrane Disease
/ genetics
Autoantigens
/ immunology
Cells, Cultured
Collagen Type IV
/ immunology
Disease Models, Animal
Female
Genetic Predisposition to Disease
Glomerulonephritis
/ genetics
HLA-DR Serological Subtypes
/ genetics
Humans
Kidney
/ drug effects
Lymphocyte Activation
Male
Mice
Mice, Knockout
Mice, Transgenic
Peptides
/ immunology
Protein Binding
Receptors, IgG
/ genetics
T-Lymphocytes
/ immunology
Anti-GBM
Glomerulonephritis
Goodpasture
HLA
HLA-DR15
PV-267
Journal
Journal of autoimmunity
ISSN: 1095-9157
Titre abrégé: J Autoimmun
Pays: England
ID NLM: 8812164
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
19
02
2019
revised:
03
05
2019
accepted:
04
05
2019
pubmed:
21
5
2019
medline:
22
8
2020
entrez:
21
5
2019
Statut:
ppublish
Résumé
Goodpasture's disease manifests as rapidly progressive glomerulonephritis. Current immunosuppressive treatments do not specifically target the pathological immune response and have significant side effects. Like most autoimmune diseases, the strongest genetic association is with the HLA alleles. Inheritance of HLA-DR15 confers susceptibility, and structure-function studies have shown that HLA-DR15 plays a causative role in activating autoreactive pro-inflammatory T cells. Thus, specific inhibition of HLA-DR15 would provide a targeted therapeutic approach. We hypothesised that PV-267, an HLA-DR15-specific inhibitor, would effectively block HLA-DR15 presentation of the dominant epitope, attenuate the activation of autoreactive T cells, and limit disease. Using humanised HLA-DR15 transgenic mice, α3
Identifiants
pubmed: 31104947
pii: S0896-8411(18)30665-6
doi: 10.1016/j.jaut.2019.05.004
pii:
doi:
Substances chimiques
Autoantigens
0
Collagen Type IV
0
Fcgr2b protein, mouse
0
HLA-DR Serological Subtypes
0
HLA-DR15 antigen
0
Peptides
0
Receptors, IgG
0
type IV collagen alpha3 chain
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102276Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.