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




Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 14:R200

First Online: 24 September 2012Received: 02 April 2012Revised: 03 June 2012Accepted: 24 September 2012

Abstract

IntroductionPsoriatic 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.

MethodsEleven 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.

ResultsIL-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.

ConclusionsConceivably, 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.

AbbreviationsACRAmerican College of Rheumatology

AMCAcademic Medical Center

CRPC-reactive protein

DAS28disease activity score

DCdendritic cell

ESRerythrocyte sedimentation rate

FLSfibroblast-like synoviocyte

HRPhorseradish peroxidase

ICHInternational Conference of Harmonization

IL-20interleukin-20

IL-20RIL-20 receptor

IODintegrated optical density

KCkeratinocytes

LFA-3lymphocyte function-associated antigen-3

PASIPsoriasis Area and Severity Index

PsApsoriatic arthritis

RArheumatoid arthritis

SJCswollen-joint count

TJCtender-joint count

TNFtumor necrosis factor

VASvisual analogue scale.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4038 contains supplementary material, which is available to authorized users.

Maria C Lebre, Christina L Jonckheere contributed equally to this work.

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Author: Maria C Lebre - Christina L Jonckheere - Maarten C Kraan - Arno WR van Kuijk - Jan D Bos - Menno de Rie - Danielle M 

Source: https://link.springer.com/







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