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Open Access Research article

Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment

Maria C Lebre12*, Christina L Jonckheere1, Maarten C Kraan13, Arno WR van Kuijk1, Jan D Bos4, Menno de Rie45, Danielle M Gerlag1 and Paul P Tak16

Author affiliations

1 Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands

2 Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands

3 AstraZeneca, Mölndal, Sweden

4 Department of Dermatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands

5 Department of Dermatology, Erasmus Medical Center, Rotterdam, The Netherlands

6 Academic Medical Center/University of Amsterdam and GlaxoSmithKline, Stevenage, UK

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Citation and License

Arthritis Research & Therapy 2012, 14:R200  doi:10.1186/ar4038

Published: 24 September 2012

Abstract

Introduction

Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement in psoriasis but has limited effectiveness in PsA. Interleukin-20 (IL-20) is a key proinflammatory cytokine involved in the pathogenesis of psoriasis. The effects of alefacept treatment on IL-20 expression in the synovium of patients with psoriasis and PsA are currently unknown.

Methods

Eleven patients with active PsA and chronic plaque psoriasis were treated with alefacept (7.5 mg per week for 12 weeks) in an open-label study. Skin biopsies were taken before and after 1 and 6 weeks, whereas synovial biopsies were obtained before and 4 and 12 weeks after treatment. Synovial biopsies from patients with rheumatoid arthritis (RA) (n = 10) were used as disease controls. Immunohistochemical analysis was performed to detect IL-20 expression, and stained synovial tissue sections were evaluated with digital image analysis. Double staining was performed with IL-20 and CD68 (macrophages), and conversely with CD55 (fibroblast-like synoviocytes, FLSs) to determine the phenotype of IL-20-positive cells in PsA synovium. IL-20 expression in skin sections (n = 6) was analyzed semiquantitatively.

Results

IL-20 was abundantly expressed in both PsA and RA synovial tissues. In inflamed PsA synovium, CD68+ macrophages and CD55+ FLSs coexpressed IL-20, and its expression correlated with the numbers of FLSs. IL-20 expression in lesional skin of PsA patients decreased significantly (P = 0.04) 6 weeks after treatment and correlated positively with the Psoriasis Area and Severity Index (PASI). IL-20 expression in PsA synovium was not affected by alefacept.

Conclusions

Conceivably, the relatively limited effectiveness of alefacept in PsA patients (compared with anti-tumor necrosis factor (TNF) therapy) might be explained in part by persistent FLS-derived IL-20 expression.