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特应性皮炎患者皮肤组织中白介素-31 的表达及意义

Itch in dermatomyositis: the role of increased skin interleukin-31.

机构信息

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, U.S.A.

Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, U.S.A.

出版信息

Br J Dermatol. 2018 Sep;179(3):669-678. doi: 10.1111/bjd.16498. Epub 2018 Jun 21.

Abstract

BACKGROUND

Interleukin (IL)-31 is implicated in pruritus associated with pruritic skin diseases like atopic dermatitis. Although pruritus is a prominent feature in dermatomyositis (DM), few studies have evaluated the pathogenesis of DM-associated itch.

OBJECTIVES

To establish the prevalence of itch in DM, and to investigate the role of IL-31 in DM-related itch.

METHODS

Pruritus and disease activity of DM were evaluated by a visual analogue scale (VAS) and the Cutaneous Disease and Activity Severity Index (CDASI), respectively. Expression of IL-31 and IL-31 receptor alpha (IL-31RA) in lesional DM, nonlesional DM and healthy control skin was evaluated by quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence. Flow cytometry was performed on skin cells isolated from lesional DM skin to identify cellular sources of IL-31 in DM.

RESULTS

Among 191 patients with DM, 50·8% had moderate-to-severe itch, and itch was correlated with increased cutaneous severity (r = 0·34). In patients with itchy DM, gene expression of IL31 and IL31RA in lesional skin was upregulated compared with nonlesional skin and healthy control skin. IL31 mRNA expression positively correlated with VAS itch score (r = 0·67). On immunofluorescence, immunoreactivity for IL-31 and IL-31RA was stronger in lesional skin. Flow cytometry showed that lesional DM skin contained significantly more IL-31-producing cells, and CD4 cells were the most common cell type. Lenabasum, an emerging treatment for DM, significantly downregulated IL-31 from CpG-stimulated peripheral blood mononuclear cells.

CONCLUSIONS

Increased skin IL-31 may play a role in DM-associated itch, and ongoing trials will evaluate the effects of systemic treatment on IL-31 and itch in DM.

摘要

背景

白细胞介素(IL)-31 参与特应性皮炎等瘙痒性皮肤病相关的瘙痒。虽然瘙痒是皮肌炎(DM)的突出特征,但很少有研究评估 DM 相关瘙痒的发病机制。

目的

确定 DM 中瘙痒的患病率,并研究 IL-31 在 DM 相关瘙痒中的作用。

方法

通过视觉模拟量表(VAS)和皮肤疾病和活动严重程度指数(CDASI)分别评估 DM 的瘙痒和疾病活动。通过定量逆转录聚合酶链反应和免疫荧光评估病变 DM、非病变 DM 和健康对照皮肤中的 IL-31 和 IL-31 受体α(IL-31RA)表达。对来自病变 DM 皮肤的皮肤细胞进行流式细胞术,以鉴定 DM 中 IL-31 的细胞来源。

结果

在 191 例 DM 患者中,50.8%有中重度瘙痒,且瘙痒与皮肤严重程度增加相关(r = 0.34)。在有瘙痒 DM 的患者中,病变皮肤中的 IL31 和 IL31RA 基因表达较非病变皮肤和健康对照皮肤上调。IL31 mRNA 表达与 VAS 瘙痒评分呈正相关(r = 0.67)。免疫荧光显示,病变皮肤中 IL-31 和 IL-31RA 的免疫反应性更强。流式细胞术显示病变 DM 皮肤中产生 IL-31 的细胞明显更多,且 CD4 细胞是最常见的细胞类型。用于治疗 DM 的新兴药物 lenabasum 可显著下调 CpG 刺激的外周血单个核细胞中的 IL-31。

结论

皮肤中 IL-31 的增加可能在 DM 相关瘙痒中起作用,正在进行的试验将评估全身治疗对 DM 中 IL-31 和瘙痒的影响。

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