Table_10_Exploration of Potential Integrated Models of N6-Methyladenosine Immunity in Systemic Lupus Erythematosus by Bioinformatic Analyses.xlsx

Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease of unknown etiology. The epigenetic regulation of N6-methyladenosine (m6A) modification in immunity is emerging. However, few studies have focused on SLE and m6A immune regulation. In this study, we aimed to explore a potential integrated model of m6A immunity in SLE. The models were constructed based on RNA-seq data of SLE. A consensus clustering algorithm was applied to reveal the m6A-immune signature using principal component analysis (PCA). Univariate and multivariate Cox regression analyses and Kaplan–Meier analysis were used to evaluate diagnostic differences between groups. The effects of m6A immune-related characteristics were investigated, including risk evaluation of m6A immune phenotype-related characteristics, immune cell infiltration profiles, diagnostic value, and enrichment pathways. CIBERSORT, ESTIMATE, and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate the relative immune cell infiltrations (ICIs) of the samples. Conventional bioinformatics methods were used to identify key m6A regulators, pathways, gene modules, and the coexpression network of SLE. In summary, our study revealed that IGFBP3 (as a key m6A regulator) and two pivotal immune genes (CD14 and IDO1) may aid in the diagnosis and treatment of SLE. The potential integrated models of m6A immunity that we developed could guide clinical management and may contribute to the development of personalized immunotherapy strategies.

系统性红斑狼疮（Systemic lupus erythematosus, SLE）是一种病因未明的典型全身性自身免疫性疾病。当前，免疫领域中N6-甲基腺苷（N6-methyladenosine, m6A）修饰的表观遗传调控研究正逐渐兴起，但针对SLE与m6A免疫调控的相关研究仍较为匮乏。本研究旨在探索SLE中m6A免疫相关的潜在整合模型，模型基于SLE的RNA测序（RNA-seq）数据构建。研究采用一致性聚类算法，并结合主成分分析（Principal Component Analysis, PCA）揭示m6A免疫特征；通过单变量与多变量Cox回归分析、Kaplan-Meier生存分析评估各组间的诊断差异。此外，本研究还探究了m6A免疫相关特征的效应，包括m6A免疫表型相关特征的风险评估、免疫细胞浸润谱、诊断价值及富集通路。本研究使用CIBERSORT、ESTIMATE以及单样本基因集富集分析（single-sample gene set enrichment analysis, ssGSEA）对样本的相对免疫细胞浸润量（immune cell infiltrations, ICIs）进行评估；并采用常规生物信息学方法鉴定关键m6A调控因子、通路、基因模块及SLE的共表达网络。综上，本研究发现胰岛素样生长因子结合蛋白3（IGFBP3，作为核心m6A调控因子）以及两个关键免疫基因CD14与IDO1，或可辅助SLE的诊断与治疗。本研究构建的m6A免疫潜在整合模型可为临床管理提供指导，并有望助力个性化免疫治疗策略的开发。