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

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.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.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.Rheumatoid arthritis (RA) is a chronic inflammatory disorder that results in severe cartilage damage and bone destruction in synovial joints. Despite unclear disease etiology, it is commonly appreciated that both genetic and environmental factors are underlying risk factors in the pathogenesis of RA. In recent years, an important role for innate immune receptors in RA has emerged, especially focused on members of the Toll-like receptor (TLR) family [1,2]. These innate responses were recently suggested to modulate and induce the autoimmune-related Th17 responses [3,4].A different class of innate immune receptors inv