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Role of Citrullinated Fibrinogen Peptides in the Activation of CD4 T Cells from Patients with Rheumatoid Arthritis

  • Shin, Kihyuk (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology) ;
  • Hong, SeokChan (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology) ;
  • Choi, Eun-Hye (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology) ;
  • Lim, Mi-Kyoung (Division of Rheumatology, Department of Internal Medicine, Eulji Medi-Bio Research Institute, Eulji University) ;
  • Shim, Seung-Cheol (Division of Rheumatology, Department of Internal Medicine, Eulji Medi-Bio Research Institute, Eulji University) ;
  • Ju, Ji-Hyeon (The Center for Rheumatic Diseases, Kangnam St. Mary's Hospital, and Rheumatism Research Center, College of Medicine, The Catholic University) ;
  • Lee, Seung-Hyo (Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology)
  • Received : 2013.06.13
  • Accepted : 2013.06.26
  • Published : 2013.08.30
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Abstract

This study was conducted to determine whether CD4 T cell responses to citrullinated fibrinogen occur in patients with rheumatoid arthritis (RA), especially in HLA-DR4-positive subjects. Whole peripheral blood mononuclear cells (PBMCs) of RA patients and control subjects were stimulated with citrullinated fibrinogen peptides, and T-cell production of proliferation and proinflammatory cytokines, such as interferon-${\gamma}$(IFN-${\gamma}$) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, $Fib-{\alpha}$ R84Cit, identified as a DRB1*0401-restricted T cell epitope in HLA-DR4 transgenic mice, and the degree of T cell activation was examined similarly. No proliferative responses to the citrullinated fibrinogen peptides were observed in whole PBMCs or CD4 T cells from RA patients. Furthermore, no increased production of IFN-${\gamma}$ or IL-17A was found in whole PBMCs or CD4 T cells stimulated with the citrullinated fibrinogen peptides, although these cells responded to recall antigen, a mixture of tetanus toxoid, purified protein derivative (PPD) from Mycobacterium tuberculosis, and Candida albicans. The results of this study indicate that anti-citrulline immunity in RA patients may be mediated by fibrinogen because there is no evidence of CD4 T cell-mediated immune responses to citrullinated fibrinogen peptides.

Keywords

References

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