Cao Jianye, Du Tiantao, Li Jian, Chen Baiyu, Xie Xianting, Zhang Guoshu, Feng Jia, Xu Tao
Clinical Medical College, Southwest Medical University, Luzhou, China.
Department of Thoracic Surgery, Hejiang County People's Hospital, Luzhou, Sichuan, China.
Front Immunol. 2024 Dec 12;15:1464479. doi: 10.3389/fimmu.2024.1464479. eCollection 2024.
Lichen planus (LP), an autoimmune disorder, remains incompletely understood in terms of its etiological mechanisms. This study aims to elucidate causal relationships among immune cell populations, plasma metabolites, and lichen planus using Mendelian randomization (MR) techniques.
Employing a two-sample, two-step MR approach, with single nucleotide polymorphisms (SNP) serving as genetic instruments for both exposures and mediators, this study minimizes biases from confounding and reverse causality. Leveraging summary statistics from genome-wide association studies (GWAS) involving 731 immune cell traits (N = 3757), 1091 plasma metabolite traits (N = 8299), and lichen planus (N = 367668), inverse variance weighting (IVW) is adopted as the primary MR analytical method. The total effect of immune cells traits on LP is decomposed into direct and indirect effects mediated by plasma metabolites.
MR analysis reveals causal associations for 28 immune cell traits and 38 plasma metabolites with LP ( < 0.05). Specifically, NK % lymphocyte shows a negatively correlated causal effect with LP (OR = 0.952; 95% CI: [0.910, 0.995], = 0.030). Among mediators, Picolinate significantly contributes, explaining 16.4% (95% CI: [28.3%, 4.54%]) of the association between NK % lymphocyte and LP.
These findings support a potential protective causal effect of NK % lymphocyte on LP, partially mediated by Picolinate levels. Thus, interventions targeting Picolinate levels may mitigate LP burden attributed to low NK % lymphocyte counts. This study provides new evidence and insights into the pathogenesis of lichen planus, advancing our understanding of its underlying mechanisms.
扁平苔藓（LP）是一种自身免疫性疾病，其病因机制尚未完全明确。本研究旨在利用孟德尔随机化（MR）技术阐明免疫细胞群体、血浆代谢物与扁平苔藓之间的因果关系。
本研究采用两样本、两步MR方法，以单核苷酸多态性（SNP）作为暴露和中介的遗传工具，最大限度地减少混杂因素和反向因果关系带来的偏差。利用来自全基因组关联研究（GWAS）的汇总统计数据，这些研究涉及731个免疫细胞特征（N = 3757）、1091个血浆代谢物特征（N = 8299）和扁平苔藓（N = 367668），采用逆方差加权（IVW）作为主要的MR分析方法。免疫细胞特征对LP的总效应被分解为由血浆代谢物介导的直接效应和间接效应。
MR分析揭示了28个免疫细胞特征和38种血浆代谢物与LP之间的因果关联（< 0.05）。具体而言，NK%淋巴细胞与LP呈负相关因果效应（OR = 0.952；95%CI：[0.910，0.995]， = 0.030）。在中介物中，吡啶甲酸有显著贡献，解释了NK%淋巴细胞与LP之间关联的16.4%（95%CI：[28.3%，4.54%]）。
这些发现支持NK%淋巴细胞对LP具有潜在的保护性因果效应，部分由吡啶甲酸水平介导。因此，针对吡啶甲酸水平的干预措施可能减轻因NK%淋巴细胞计数低而导致的LP负担。本研究为扁平苔藓的发病机制提供了新的证据和见解，增进了我们对其潜在机制的理解。
