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TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to TNF blockade
  1. Arno W R van Kuijk (a.w.vankuijk{at}amc.uva.nl)
  1. Academic Medical Centre/University of Amsterdam, Netherlands
    1. Carla A Wijbrandts (c.a.wijbrandts{at}amc.uva.nl)
    1. Academic Medical Centre/University of Amsterdam, Netherlands
      1. Marjolein Vinkenoog (m.vinkenoog{at}amc.uva.nl)
      1. Academic Medical Centre/University of Amsterdam, Netherlands
        1. Timothy S Zheng (timothy.zheng{at}biogenidec.com)
        1. Biogen Idec, MA, United States
          1. Kris A Reedquist (k.a.reedquist{at}amc.uva.nl)
          1. Academic Medical Centre/University of Amsterdam, Netherlands
            1. Paul P Tak (p.p.tak{at}amc.uva.nl)
            1. Academic Medical Centre/University of Amsterdam, Netherlands

              Abstract

              Objective: To investigate the expression of TNF like weak inducer of apoptosis (TWEAK) and its receptor Fn14 in the inflamed synovium of patients with arthritis, as TWEAK blockade had a beneficial effect in an animal model of RA.

              Methods: Synovial tissue (ST) biopsies were obtained from 6 early, methotrexate naive RA patients as well as 13 RA patients and 16 patients with psoriatic arthritis (PsA) who were matched for treatment and disease duration. Serial ST samples were obtained from a separate cohort of 13 RA patients before and after infliximab treatment. TWEAK and Fn14 expression was evaluated by immunohistochemistry and digital image analysis.

              Results: TWEAK and Fn14 were clearly expressed in ST of RA and PsA patients. TWEAK expression was significantly higher in RA (sub)lining compared to PsA (P = 0.005 and P = 0.014, respectively), but Fn14 expression was comparable. Double immunofluorescence showed TWEAK and Fn14 expression on fibroblast-like synoviocytes and macrophages, but not T cells. Of interest, persistent TWEAK and Fn14 expression was found after anti-TNF therapy.

              Conclusions: TWEAK and Fn14 are abundantly expressed in the inflamed synovium of RA and PsA patients. This raises the possibility that blocking TWEAK/Fn14 signalling could be of therapeutic benefit in inflammatory arthritis.

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