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Báo cáo y học: "Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by imaging surface plasmon resonance"

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: Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by imaging surface plasmon resonance. | van Beers et al. Arthritis Research Therapy 2010 12 R219 http arthritis-research.eom content 12 6 R219 RESEARCH ARTICLE Open Access Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by imaging surface plasmon resonance 1 f 2f 1 1 Joyce JBC van Beers Reinout Raijmakers Lou-Ella Alexander Judith Stammen-Vogelzangs Angelique MC Lokate1 Albert JR Heck2 Richard BM Schasfoort3 4 Ger JM Pruijn1 Abstract Introduction Rheumatoid arthritis RA frequently involves the loss of tolerance to citrullinated antigens which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA its autoepitopes were systematically mapped using a new methodology. Methods Human fibrinogen was citrullinated in vitro by peptidylarginine deiminases PAD subjected to proteolysis and the resulting peptides were fractionated by ion exchange chromatography. The peptide composition of the citrullinated peptide-containing fractions was determined by high resolution tandem mass spectrometry. The recognition of these fractions by patient sera was subsequently analyzed by imaging surface plasmon resonance on microarrays. Results In total about two-thirds of the 81 arginines of human fibrinogen were found to be susceptible to citrullination by the human PAD2 the human PAD4 or the rabbit PAD2 enzymes. Citrullination sites were found in all three polypeptide chains of fibrinogen although the a-chain appeared to contain most of them. The analysis of 98 anti-citrullinated protein antibody-positive RA sera using the new methodology allowed the identification of three major citrullinated epitope regions in human fibrinogen two in the a- and one in the p-chain. Conclusions A comprehensive overview of citrullination sites in human fibrinogen was generated. The multiplex analysis of peptide fractions derived from a .