Qiao Shan, Wang Jia, Zhang Shan-Chao, Wang Ai-Hua, Li Hai-Yun, Xin Tao
Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
Post-Doctoral Scientific Research Station, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Front Neurol. 2025 May 9;16:1568274. doi: 10.3389/fneur.2025.1568274. eCollection 2025.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a critical neurological disorder mediated by autoimmune mechanisms, Previous literature suggests that immune inflammatory responses may be involved in the progression of anti NMDAR encephalitis, but its molecular regulatory mechanisms still remain uncertain. We aimed to identify transcriptome-wide landscape of mRNAs and explore the potential pathogenesis for anti-NMDAR encephalitis.
Peripheral blood mononuclear cells were obtained from six patients with anti-NMDAR encephalitis and six controls for RNA extraction and library creation. The Illumina HiSeq platform was used to do transcriptome sequencing. We utilized R software to identify differentially expressed genes (DEGs) and performed a functional enrichment analysis. Furthermore, random forest (RF) and support vector machine-recursive feature elimination (SVM-RFE) were employed to screen for and identify anti-NMDAR encephalitis diagnostic signatures. To verify the findings, we employed quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were utilized to assess the diagnostic values. We evaluated the inflammatory state of anti-NMDAR encephalitis using cell-type identification by computing the relative subsets of RNA transcripts (CIBERSORT) and investigated the relationship between diagnostic biomarkers and immune cell subsets.
899 DEGs were identified (568 upregulated and 331 downregulated), of which 78 were immune-related genes. The DEGs were found to be considerably enriched in immunological inflammation-related pathways, according to the functional enrichment analysis. Insulin-like factor 3 [area under the curve (AUC) = 0.917] and tumor protein translationally controlled regulator 1 (AUC = 0.944) were considered potential diagnostic indicator candidates of anti-NMDAR encephalitis, with statistically significant variations in expression. An immune cell analysis of immune cell proportions suggests that monocytes, CD8 T cells, and T regulatory cells may all be involved in the development of anti-NMDAR encephalitis.
Transcriptome analysis reveals significant activation of peripheral immune-inflammatory pathways in anti-NMDAR encephalitis. INSL3 and TPT1 may serve as potential auxiliary diagnostic biomarkers, while monocyte, CD8+ T cell, and Treg infiltration likely synergistically drive disease progression.
抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎是一种由自身免疫机制介导的严重神经系统疾病。以往文献表明，免疫炎症反应可能参与抗NMDAR脑炎的进展，但其分子调控机制仍不明确。我们旨在确定全转录组范围内的mRNA图谱，并探索抗NMDAR脑炎的潜在发病机制。
从6例抗NMDAR脑炎患者和6例对照者中获取外周血单个核细胞，用于RNA提取和文库构建。使用Illumina HiSeq平台进行转录组测序。我们利用R软件鉴定差异表达基因（DEG），并进行功能富集分析。此外，采用随机森林（RF）和支持向量机递归特征消除（SVM-RFE）筛选和鉴定抗NMDAR脑炎诊断标志物。为验证结果，我们采用定量实时聚合酶链反应。利用受试者工作特征曲线评估诊断价值。我们通过计算RNA转录本的相对亚群（CIBERSORT）来鉴定细胞类型，从而评估抗NMDAR脑炎的炎症状态，并研究诊断生物标志物与免疫细胞亚群之间的关系。
共鉴定出899个DEG（568个上调和331个下调），其中78个为免疫相关基因。功能富集分析发现，DEG在免疫炎症相关通路中显著富集。胰岛素样因子3[曲线下面积（AUC）=0.917]和肿瘤蛋白翻译调控因子1（AUC = 0.944）被认为是抗NMDAR脑炎潜在的诊断指标候选物，其表达存在统计学显著差异。对免疫细胞比例的免疫细胞分析表明，单核细胞、CD8 T细胞和调节性T细胞可能均参与抗NMDAR脑炎的发病过程。
转录组分析显示抗NMDAR脑炎外周免疫炎症通路显著激活。INSL3和TPT1可能作为潜在的辅助诊断生物标志物，而单核细胞、CD8 + T细胞和Treg浸润可能协同推动疾病进展。
