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Comparative Study
. 2010 Jan;69(1):301-4.
doi: 10.1136/ard.2008.090548.

TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to tumour necrosis factor blockade

A W R van Kuijk  1 , C A Wijbrandts, M Vinkenoog, T S Zheng, K A Reedquist, P P Tak
Affiliations
Comparative Study

TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to tumour necrosis factor blockade

A W R van Kuijk et al. Ann Rheum Dis. 2010 Jan.

Abstract

Objective: To investigate the expression of tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) in the inflamed synovium of patients with arthritis, as TWEAK blockade has been observed to have a beneficial effect in an animal model of rheumatoid arthritis (RA).

Methods: Synovial tissue (ST) biopsies were obtained from 6 early, methotrexate-naive patients with RA as well as 13 patients with RA 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 patients with RA 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 patients with RA and PsA. TWEAK expression was significantly higher in RA (sub)lining samples 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 patients with RA and PsA. This raises the possibility that blocking TWEAK/Fn14 signalling could be of therapeutic benefit in inflammatory arthritis.

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Conflict of interest statement

Competing interests: TSZ is an employee of Biogen Idec, Cambridge, Massachusetts, USA.

Figures

Figure 1
Figure 1
Representative photographs showing tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) expression (reddish-brown staining) in rheumatoid arthritis (RA) synovial tissue (ST) (a–c) and psoriatic arthritis (PsA) ST (d–f). Overview of RA ST (a) (original magnification 100×), and close up of the intimal lining layer (b) and the synovial sublining with (peri)vascular staining (c) (magnification 200×); overview of PsA ST (d), and close up of the intimal lining layer (e) and the synovial sublining with (peri)vascular staining (f).
Figure 2
Figure 2
Representative photographs showing tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) receptor fibroblast growth factor inducible 14 (Fn14) expression (reddish-brown staining) in rheumatoid arthritis (RA) synovial tissue (ST) (a–c) and psoriatic arthritis (PsA) synovial tissue (d–f). Overview of RA ST (a) (original magnification 100×), and close up of the intimal lining layer (b) and the synovial sublining (c) (magnification 200×); overview of PsA ST (d), and close up of the intimal lining layer (e) and the synovial sublining (f).
See this image and copyright information in PMC

References

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