tailieunhanh - Báo cáo y học: "Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis. | Plantinga et al. Arthritis Research Therapy 2010 12 R26 http content 12 1 R26 RESEARCH ARTICLE Open Access Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis Theo S Plantings1 2 Jaap Fransen3 Nozomi Takahashi4 5 6 Rinke Stienstra1 2 Piet L van Riel3 Wim B van den Berg4 Mihai G Netea1 2 Leo AB Joosten1 2 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 .