评估循环血浆蛋白、731 种免疫细胞表型与特应性皮炎之间的因果关系:调解孟德尔随机化研究。

IF 2.5 4区 医学 Q3 ALLERGY
Wenjing Zhang, Shanshan Wei, Qian Li, Li Yin, Junhao Zhu, Shan Yang, Silang Zhu, Kuan Lai
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引用次数: 0

摘要

简介特应性皮炎(AD)是一种以湿疹和剧烈瘙痒为特征的慢性炎症性皮肤病。然而,其发病机制尚未完全阐明。本研究旨在探讨血浆蛋白与过敏性皮炎之间的因果关系,并确定和量化免疫细胞表型作为介质的潜在作用:我们利用全基因组关联研究的汇总级数据,进行了涉及4907种循环血浆蛋白、731种免疫细胞表型和AD的双样本孟德尔随机化(MR)分析。首先,我们进行了双向单变量 MR 分析,以预测循环血浆蛋白与 AD 之间的因果效应。随后,我们采用了两步式磁共振分析来仔细研究可能介导这些效应的免疫细胞表型。反方差加权是 MR 分析的主要方法,而 Cochran's Q 检验和 MR-Egger 截距检验则分别用于评估异质性和多义性的存在。然后,我们使用 "leave-one-out "检验来确定结果是否会受到单个单核苷酸多态性的影响:结果发现:KRT1、IL18R1和SEMA6A与AD风险呈正相关,而BDH2、ADAMTS3、ANKRD1、TIAM1、MID2和IFNA16均与AD风险呈负相关。中介分析表明,CM CD8br细胞上的CD8是IFNA16与AD之间的中介,中介效应比例为11.2%。此外,敏感性分析也没有发现显著的异质性或水平多向性:我们的研究结果表明,循环血浆蛋白 IFNA16 与 AD 之间存在单向因果关系。这项研究还探索了可能作为介质的免疫细胞表型,为了解 AD 的病因、发病机制和潜在的临床干预措施提供了新的视角。然而,这些发现还需要临床和实验室研究来验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluating the Causal Association between Circulating Plasma Proteins, 731 Immune Cell Phenotypes, and Atopic Dermatitis: A Mediation Mendelian Randomization Study.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and severe itching. However, its pathogenesis has not yet been fully elucidated. The aim of this study was to investigate the causal relationship between plasma proteins and AD, as well as to identify and quantify the potential roles of immune cell phenotypes as mediators.

Methods: We utilized summary-level data from genome-wide association studies and conducted a two-sample Mendelian randomization (MR) analysis involving 4,907 circulating plasma proteins, 731 immune cell phenotypes, and AD. Initially, we conducted bidirectional univariate MR analyses to forecast causal effects linking circulating plasma proteins and AD. Subsequently, we employed a two-step MR analysis to scrutinize the immune cell phenotypes that could mediate these effects. The inverse variance weighted was the main method employed for MR analysis, while the Cochran's Q test and MR-Egger intercept test were used to assess the presence of heterogeneity and pleiotropy, respectively. We then determined whether our results could be influenced by individual single-nucleotide polymorphisms using the "leave-one-out" test.

Results: Positive correlations were observed between KRT1, IL18R1, and SEMA6A and the risk of AD, whereas BDH2, ADAMTS3, ANKRD1, TIAM1, MID2, and IFNA16 all showed negative correlations with the risk of AD. Mediation analysis indicated that CD8 on CM CD8br cells acted as a mediator between IFNA16 and AD, with a mediation effect proportion of 11.2%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy.

Conclusion: Our findings indicated the presence of a one-way causal relationship between the circulating plasma protein IFNA16 and AD. This study also explored immune cell phenotypes that may serve as mediators, offering novel insights into the etiology, pathogenesis, and potential clinical interventions in AD. Nevertheless, these findings need to be validated by clinical and laboratory studies.

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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
105
审稿时长
2 months
期刊介绍: ''International Archives of Allergy and Immunology'' provides a forum for basic and clinical research in modern molecular and cellular allergology and immunology. Appearing monthly, the journal publishes original work in the fields of allergy, immunopathology, immunogenetics, immunopharmacology, immunoendocrinology, tumor immunology, mucosal immunity, transplantation and immunology of infectious and connective tissue diseases.
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