银屑病关节炎患者滑膜和皮损中白细胞介素-20的表达：对阿法赛特治疗的不同反应

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

作者信息

Lebre Maria C, Jonckheere Christina L, Kraan Maarten C, van Kuijk Arno W R, Bos Jan D, de Rie Menno, Gerlag Danielle M, Tak Paul P

出版信息

Arthritis Res Ther. 2012 Sep 24;14(5):R200. doi: 10.1186/ar4038.

DOI:10.1186/ar4038

PMID:23006144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3580512/

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.

摘要

引言

银屑病关节炎（PsA）是一种与银屑病相关的炎性关节疾病。阿法赛特（一种与淋巴细胞功能相关抗原（LFA）-3 Ig融合蛋白，可与CD2结合并作为T细胞活化的拮抗剂）已被证明可改善银屑病，但对PsA的疗效有限。白细胞介素-20（IL-20）是参与银屑病发病机制的关键促炎细胞因子。目前尚不清楚阿法赛特治疗对银屑病和PsA患者滑膜中IL-20表达的影响。

方法

在一项开放标签研究中，11例活动性PsA和慢性斑块状银屑病患者接受阿法赛特治疗（每周7.5mg，共12周）。在治疗前、治疗1周和6周后进行皮肤活检，而在治疗前、治疗4周和12周后获取滑膜活检样本。将类风湿关节炎（RA）患者（n = 10）的滑膜活检样本用作疾病对照。进行免疫组织化学分析以检测IL-20表达，并使用数字图像分析对染色的滑膜组织切片进行评估。用IL-20和CD68（巨噬细胞）进行双重染色，反之用CD55（成纤维样滑膜细胞，FLS）进行双重染色，以确定PsA滑膜中IL-20阳性细胞的表型。对皮肤切片（n = 6）中的IL-20表达进行半定量分析。

结果

IL-20在PsA和RA滑膜组织中均大量表达。在炎性PsA滑膜中，CD68 +巨噬细胞和CD55 + FLS共同表达IL-20，其表达与FLS数量相关。PsA患者皮损皮肤中IL-20表达在治疗6周后显著降低（P = 0.04），且与银屑病面积和严重程度指数（PASI）呈正相关。阿法赛特不影响PsA滑膜中IL-20的表达。