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横断面研究中斑秃中重度患者的血液生物标志物显示全身性免疫和心血管生物标志物失调。

Cross-sectional study of blood biomarkers of patients with moderate to severe alopecia areata reveals systemic immune and cardiovascular biomarker dysregulation.

机构信息

Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.

Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York.

出版信息

J Am Acad Dermatol. 2021 Feb;84(2):370-380. doi: 10.1016/j.jaad.2020.04.138. Epub 2020 May 4.

DOI:10.1016/j.jaad.2020.04.138
PMID:32376430
Abstract

BACKGROUND

Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile.

OBJECTIVE

To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity.

METHODS

In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49).

RESULTS

Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate, <.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P < .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P < .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy.

LIMITATIONS

Our analysis was limited to 350 proteins.

CONCLUSION

This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches.

摘要

背景

尽管基于头皮组织的研究,人们对斑秃(AA)发病机制的理解有所增加,但对其全身特征知之甚少。

目的

评估 AA 的血液蛋白质组特征,并确定与疾病严重程度增加相关的生物标志物。

方法

在一项横断面研究中,我们使用 OLINK 高通量蛋白质组学评估了 350 种炎症和心血管蛋白,包括 35 名中重度 AA 患者(n=35)、36 名健康个体、19 名中重度银屑病患者和 49 名特应性皮炎患者。

结果

AA 患者与对照组个体之间有 74 种蛋白表达显著差异(错误发现率,<0.05),包括先天免疫(白细胞介素[IL]6/IL-8)、Th1(干扰素[IFN]γ/CXCL9/CXCL10/CXCL11)、Th2(CCL13/CCL17/CCL7)、Th17(CCL20/PI3/S100A12)和心血管风险蛋白(OLR1/OSM/MPO/PRTN3)。86 种生物标志物与 AA 临床严重程度相关(P<0.05),包括 Th1/Th2 以及心血管/动脉粥样硬化相关蛋白,包括 SELP/PGLYRP1/MPO/IL-18/OSM(P<0.05)。与健康个体相比,甚至与特应性皮炎患者和银屑病患者相比,患有 AA 全秃/普秃的患者表现出最高的全身炎症反应,包括心血管风险生物标志物。在合并特应性的情况下,AA 谱显示出一些 Th1/Th2 差异。

局限性

我们的分析仅限于 350 种蛋白。

结论

本研究定义了中重度 AA 及相关循环生物标志物的异常。它表明 AA 存在全身免疫、心血管和动脉粥样硬化生物标志物失调,这表明需要采用全身性治疗方法。

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