Identification of novel biomarkers for lupus nephritis.

0 MEDICINE, RESEARCH & EXPERIMENTAL Biomolecules & biomedicine Pub Date : 2025-01-14 DOI:10.17305/bb.2024.10450
Zhengyue Liao, Liying He, Jiaojiao Fu, Xiaotong Zhou, Yong Li, Jing He, Yixin Liu, Jinlin Guo, Sijing Liu
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Abstract

Lupus nephritis (LN) is an autoimmune disease that rapidly progresses as a secondary consequence of systemic lupus erythematosus (SLE) and has a very poor prognosis. Therefore, this study aimed to identify characteristics of immune cell infiltration and investigate potential therapeutic targets using bioinformatics methods and the Murphy Roths Large/lymphoproliferation (MRL/lpr) mouse model. In this study, a total of 2,810 differentially expressed genes (DEGs) were identified, which were primarily enriched in inflammatory and immune regulation pathways. From these DEGs, 226 immune-related genes (IRGs) were also identified. The single-sample gene set enrichment analysis (ssGSEA) revealed that patients with LN had increased infiltration of effector memory CD4+ T cells, effector memory CD8+ T cells, gamma delta T cells, myeloid-derived suppressor cells (MDSC), follicular helper T cells, Th1 cells, and Th2 cells, and this was closely correlated with the DEG-IRGs. Furthermore, the potential therapeutic biomarkers, CD244, S100 calcium binding protein P (S100P), and vascular endothelial growth factor C (VEGFC), were identified by Random Forest Approach (RFA), which were validated in LN mice. These findings provide new evidence and insights for further research on diagnosis and treatment of LN by identifying critical genes and their associations with immune infiltration.

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鉴定狼疮性肾炎的新型生物标记物。
狼疮性肾炎(LN)是一种继发于系统性红斑狼疮(SLE)的自身免疫性疾病,病情发展迅速,预后极差。因此,本研究旨在利用生物信息学方法和墨菲罗氏大细胞/淋巴细胞增生(MRL/lpr)小鼠模型,确定免疫细胞浸润的特征并研究潜在的治疗靶点。本研究共鉴定出2810个差异表达基因(DEG),这些基因主要富集在炎症和免疫调节通路中。在这些 DEGs 中,还发现了 226 个免疫相关基因(IRGs)。单样本基因组富集分析(ssGSEA)显示,LN患者的效应记忆CD4+ T细胞、效应记忆CD8+ T细胞、γδT细胞、髓源抑制细胞(MDSC)、滤泡辅助T细胞、Th1细胞和Th2细胞浸润增加,这与DEG-IRGs密切相关。此外,随机森林法(Random Forest Approach, RFA)鉴定出了潜在的治疗生物标志物--CD244、S100钙结合蛋白P(S100P)和血管内皮生长因子C(VEGFC),并在LN小鼠中进行了验证。这些发现通过确定关键基因及其与免疫浸润的关系,为进一步研究 LN 的诊断和治疗提供了新的证据和见解。
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