解析全身性细胞因子与六种炎症性皮肤病之间的因果关联。

Unraveling the causal associations between systemic cytokines and six inflammatory skin diseases.

作者信息

Liu Waner, Zhang Xu, Chen Xiang

机构信息

Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

出版信息

Cytokine. 2025 Jan;185:156810. doi: 10.1016/j.cyto.2024.156810. Epub 2024 Dec 3.

DOI:10.1016/j.cyto.2024.156810

PMID:39631262

Abstract

BACKGROUND

Previous observational studies have reported that systemic cytokines are associated with the risk of inflammatory skin diseases, but their conclusions remain controversial.

METHOD

We conducted a two-sample Mendelian randomization analysis to assess the relationship between systemic cytokines and six inflammatory skin disorders (including alopecia areata (AA), acne, atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis (PS) and vitiligo), based on datasets from EArly Genetics and Lifecourse Epidemiology (EAGLE) eczema consortium, acne GWAS conducted by Maris Teder Laving et al., IEU Open GWAS, and FinnGen database. Inverse-variance weighted (IVW) method was conducted in primary MR analysis, and supplemented by MR-Egger, weighted median, weighted mode, and MR-PRESSO.

RESULTS

By integrating the findings from both primary and sensitivity analyses, we identified ten systemic cytokines linked to the risk of six skin diseases using the IVW method. Briefly, four cytokines increased the risk of corresponding skin diseases: β-nerve growth factor (β-NGF) to AA (p = 0.005) and HS (p = 0.001), interleukin-8 (p = 0.014) to acne; interleukin-5 (p = 0.042) to AD; interleukin-13 (p = 0.049) to PS. In the meantime, seven cytokines could have protective effect on specific skin diseases: interleukin-9 (p = 0.040) and interleukin-2 receptor subunit alpha (IL-2ra) (p = 0.020) on AA; macrophage inflammatory protein (MIP)-1β (p = 0.020) on acne; monokine induced by IFN-γ (p = 0.006) on AD; interleukin-16 (p = 0.038), MIP-1β (p = 0.017) and IL-2ra (p = 0.020) on PS.

CONCLUSIONS

This study reveals 13 causal associations between systemic cytokines and 6 skin diseases, offering new perspectives on the prevention and management of widespread inflammatory skin disorders.

摘要

背景

既往观察性研究报告称，全身细胞因子与炎症性皮肤病风险相关，但其结论仍存在争议。

方法

我们基于早期遗传学与生命历程流行病学（EAGLE）湿疹联盟、玛丽斯·泰德·拉文等人开展的痤疮全基因组关联研究（GWAS）、IEU开放GWAS以及芬兰基因数据库的数据，进行了一项两样本孟德尔随机化分析，以评估全身细胞因子与六种炎症性皮肤病（包括斑秃（AA）、痤疮、特应性皮炎（AD）、化脓性汗腺炎（HS）、银屑病（PS）和白癜风）之间的关系。主要孟德尔随机化分析采用逆方差加权（IVW）方法，并辅以MR-Egger、加权中位数、加权模式和MR-PRESSO方法。

结果

通过整合主要分析和敏感性分析的结果，我们使用IVW方法确定了十种与六种皮肤病风险相关的全身细胞因子。简而言之，四种细胞因子增加了相应皮肤病的风险：β-神经生长因子（β-NGF）与斑秃（p = 0.005）和化脓性汗腺炎（p = 0.001）、白细胞介素-8与痤疮（p = 0.014）、白细胞介素-5与特应性皮炎（p = 0.042）、白细胞介素-13与银屑病（p = 0.049）。同时，七种细胞因子可能对特定皮肤病具有保护作用：白细胞介素-9（p = 0.040）和白细胞介素-2受体α亚基（IL-2ra）（p = 0.020）对斑秃、巨噬细胞炎性蛋白（MIP）-1β（p = 0.020）对痤疮、γ干扰素诱导的单核因子（p = 0.006）对特应性皮炎、白细胞介素-16（p = 0.038）、MIP-1β（p = 0.017）和IL-2ra（p = 0.020）对银屑病。