Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for therapy

Arno W.R. van Kuijk ^1*, Petra Reinders-Blankert ², Tom J.M. Smeets ¹, Ben A.C. Dijkmans ³ and Paul P. Tak ¹

¹ Academic Medical Center/University of Amsterdam, Netherlands
² Academic Medical Center, Netherlands
³ VU University Medical Center, Netherlands

^* To whom correspondence should be addressed. E-mail: a.w.vankuijk{at}amc.uva.nl.

Accepted 15 May 2006

Abstract

Objective: The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis (PsA). Identification of pro- inflammatory molecules in the synovium may help to identify potentially therapeutic targets. Therefore, we performed a study investigating extensively the features of cell infiltration and expression of mediators of inflammation and joint destruction in the synovium of PsA patients compared with rheumatoid arthritis (RA) patients matched for disease duration and use of medication.

Methods: Multiple synovial tissue biopsies were obtained by arthroscopy from an inflamed joint in 19 patients with PsA (8 oligoarthritis, 11 polyarthritis) and 24 patients with RA. Biopsy specimens were analyzed by immunohistochemistry to detect T cells, plasma cells, fibroblast-like synoviocytes, macrophages, pro- inflammatory cytokines, matrix metalloproteinases and tissue inhibitor metalloproteinase-1, adhesion molecules and vascular markers. Stained sections were evaluated by digital image analysis.

Results: The synovial infiltrate of PsA and RA patients was comparable with regard to numbers of fibroblast-like synoviocytes and macrophages. T cell numbers were significantly lower in the synovium of PsA patients. The number of plasma cells also tended to be lower in PsA. The expression of TNF-alpha, IL-1beta, IL- 6 and IL-18 was in PsA as high as in RA. The expression of MMPs, adhesion molecules, and vascular markers was comparable for PsA and RA.

Conclusion: These data demonstrate increased pro- inflammatory cytokine expression in PsA synovium, comparable with results obtained in RA, and support the notion that in addition to TNF-alpha blockade, there may be a rationale for therapies directed at IL-1beta, IL-6 and IL-18.

Keywords: cytokines, psoriatic arthritis, rheumatoid arthritis, synovium

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