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Arthritis Research and Therapy

, 12:R26

First Online: 16 February 2010Received: 04 August 2009Revised: 27 November 2009Accepted: 16 February 2010

Abstract

IntroductionDectin-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.

MethodsDectin-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.

ResultsEvaluation 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.

ConclusionsAlthough 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.

AbbreviationsELISAenzyme-linked immunosorbent assay

OAosteoarthritis

PBMCsperipheral blood mononuclear cells

RArheumatoid arthritis

TLRToll-like receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar2933 contains supplementary material, which is available to authorized users.

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Autor: Theo S Plantinga - Jaap Fransen - Nozomi Takahashi - Rinke Stienstra - Piet L van Riel - Wim B van den Berg - Mihai G N

Fuente: https://link.springer.com/







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