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Spring 2013, Vol. 21 No. 1

Hong Kong J. Dermatol. Venereol. (2013) 21, 5-13


Original Article

The changes in expression of Ki-67, and CD31 in psoriatic lesions before and after etanercept treatment

牛皮癬皮損在生物製劑依那西普治療前後的Ki-67及CD31 表現水平變化

B Tursen, T Kara, U Tursen, DD Apa, O Gubur, TI Kaya

Abstract

Background: Although the effectiveness of etanercept in the treatment of psoriasis is very well-established, the mechanism of action is poorly understood. It was suggested that the therapeutic effect of etanercept in psoriasis could be mediated by the inhibition of TNF expression. Although clinical trials have sometimes demonstrated a dramatic response to TNFα inhibition, only a few studies have examined the changes occuring in the skin upon TNFα inhibition. Objectives: The aim of our study was to investigate the different effects of etanercept on cell proliferation, inflammatory infiltrate, and angiogenesis in psoriasis, and to clarify the mechanism by which etanercept exerts its therapeutic effects. Methods: Clinical response, the morpho-phenotypic changes, epidermal thickness, mitotic count were analysed and the expression of CD31, proliferative marker as Ki-67, were evaluated by immunohistochemical techniques in lesional psoriatic epidermis, before and after treatment with etanercept in 11 patients. Results: In post-treatment biopsies, a decrease in the degree of epidermal hyperplasia and a significant reduction in the severity of the inflammmatory infiltrate (p<0.05) were observed. In addition, CD31 expression was significantly decreased in the dermal cellular infiltrate, (p<0.05). Ki67 expression was significantly suppressed concurrently in about 90% of cases (p<0.01). Conclusions: We suggest that etanercept may have an inhibitory effect on an initial integral component of the pathways that leads to psoriasis. Immunopharmacologic intervention in inflammatory event has the potential to improve psoriasis. Inhibition of neovascularisation may be another mechanism of action of etanercept.

背景:雖然依那西普治療牛皮癬的功效眾所周知,但當中的作用機制卻所知甚少。有專家認為依那西普治療牛皮癬的療效,可能來自通過對腫瘤壞死因子表達抑制的調節。雖然臨床試驗不時展示α腫瘤壞死因子抑制的顯著療效,但只有少數研究曾探究當中α腫瘤壞死因子抑制在皮膚上所造成的變化。目標:本研究的目的是調查依那西普在牛皮癬治療中對細胞增殖、炎性滲入和血管生成的不同效果,並闡明依那西普的治療效果是取決於那一種機制。方法:本研究對 十一名接受依那西普治療的牛皮癬患者,進行治療前後的表皮皮損分析,當中包括臨床反應、形態表現的變化、表皮厚度和核分裂數,並使用免疫組織化學 技術探測皮損當中的CD31及細胞增殖標記Ki-67的表現水平。結果:在治療後的活檢樣本中,可見表皮增生減少,而炎性滲入嚴重程度更是大幅減少(p<0.05)。此外,皮膚細胞滲入中的CD31表現水平明顯下降(p<0.05)。同時,約九成患者的Ki67表現水平,受到顯著抑制(p<0.01)。結論:我們認為依那西普可能對牛皮癬初始形成過程中的元件有著抑制作用。在牛皮癬炎症過程中,免疫藥理的干預有著潛在的治療價值。此外,抑制新生血管形成亦可能是依那西普的另一作用機制。

Keywords: CD31, Etanercept, Ki-67, psoriasis

關鍵詞: CD31,依那西普,Ki-67,牛皮癬