The down-regulation of HLA-DM gene expression in rheumatoid arthritis is not related to their promoter polymorphism.
J Immunol
; 165(9): 4861-9, 2000 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-11046010
ABSTRACT
HLA-DM molecule, a class II-like heterodimer, is a critical factor of HLA class II-dependent Ag presentation. It acts as a molecular chaperone and also functions as a peptide editor favoring the presentation of high-stability peptides. Thus, it appears to skew the peptide repertoire presented to T cells. Variation in HLA-DM expression has considerable effect on Ag presentation and regulation of these genes is likely to be a prerequisite to prevent autoimmunity. In this study, rheumatoid arthritis (RA) was chosen as a model of human autoimmune disease since its genetic susceptibility is known to be associated with the HLA-DR and -DM components. We described a limited nucleotide polymorphism in the HLA-DM promoters with functional impact on basal transcriptional activity and IFN-gamma induction as assessed in vitro. However, no difference of allele frequencies was found between controls and RA patients. Despite of this lack of association, expression of HLA-DM molecules was also investigated. Interestingly, an underexpression of HLA-DM transcripts and protein was shown in peripheral blood B cells from RA patients compared with controls or inflammatory arthritis patients. This underexpression does not affect HLA-DR genes and is responsible for a decrease of the DMDR ratio in RA patients. This specific HLA-DM down-regulation is likely to have important consequences on Ag presentation and could participate in the autoimmune process in RA.
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Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Antígenos HLA-D
/
Antígenos de Histocompatibilidade Classe II
/
Regulação para Baixo
/
Regiões Promotoras Genéticas
/
Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article