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Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis.


ABSTRACT: INTRODUCTION: Dectin-1, a pattern recognition receptor expressed by the innate immune system, is known to be a major receptor inducing Th17-type adaptive immune responses that have been demonstrated to mediate autoimmunity. In this study, dectin-1 mRNA and protein expression, as well as the recently characterized DECTIN-1 Y238X early stop codon polymorphism, were studied in relation to rheumatoid arthritis (RA) susceptibility and severity. METHODS: Dectin-1 mRNA expression was measured in synovial tissue specimens of RA, osteoarthritis (OA), and nonrheumatic patients. Dectin-1 protein expression and localization were assessed in RA synovial tissue specimens. Macrophages from individuals with different DECTIN-1 genotypes were examined for differences in cytokine responses on dectin-1 stimulation. Furthermore, clinical parameters of inflammation and bone destruction of 262 RA patients were correlated with the presence of the DECTIN-1 Y238X polymorphism. RESULTS: Evaluation of dectin-1 mRNA expression in synovial tissue biopsies revealed an increased expression in RA specimens, compared with biopsies from OA and nonrheumatic patients. Accordingly, dectin-1 protein expression in RA synovial tissue biopsies was moderate to high, especially on macrophage-like cells. Cytokine production capacity of macrophages bearing the DECTIN-1 Y238X polymorphism was demonstrated to be impaired on dectin-1 stimulation. However, the presence of the DECTIN-1 Y238X polymorphism was not associated with RA susceptibility or disease severity. CONCLUSIONS: Although expression of dectin-1 was high in synovial tissue of RA patients, and reduced cytokine production was observed in macrophages of individuals bearing the DECTIN-1 Y238X polymorphism, loss of one functional allele of DECTIN-1 is not associated with either susceptibility to or severity of RA.

SUBMITTER: Plantinga TS 

PROVIDER: S-EPMC2875660 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis.

Plantinga Theo S TS   Fransen Jaap J   Takahashi Nozomi N   Stienstra Rinke R   van Riel Piet L PL   van den Berg Wim B WB   Netea Mihai G MG   Joosten Leo Ab LA  

Arthritis research & therapy 20100216 1


<h4>Introduction</h4>Dectin-1, a pattern recognition receptor expressed by the innate immune system, is known to be a major receptor inducing Th17-type adaptive immune responses that have been demonstrated to mediate autoimmunity. In this study, dectin-1 mRNA and protein expression, as well as the recently characterized DECTIN-1 Y238X early stop codon polymorphism, were studied in relation to rheumatoid arthritis (RA) susceptibility and severity.<h4>Methods</h4>Dectin-1 mRNA expression was measu  ...[more]

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