背景:早发性精神分裂症(EOS)是一种精神分裂症(SCZ),发病年龄<18岁。炎症免疫系统异常可能参与了SCZ的发生和发展。我们旨在鉴定EOS的免疫特征基因和细胞,并从免疫学的角度进一步探讨EOS的发病机制。
方法:我们从外周血单核细胞(PBMC)的全基因组mRNA表达中获得了微阵列数据;涉及19例EOS患者(年龄范围:14.79±1.90)和18例健康对照(HC)(年龄范围:15.67±2.40)。我们使用Limma软件包筛选差异表达基因(DEGs),并使用加权基因共表达网络分析(WGCNA)筛选模块基因。此外,识别免疫特征基因和细胞,我们进行了富集分析,免疫浸润分析,和接收机工作特性(ROC)曲线分析;我们还使用了随机森林(RF),支持向量机(SVM),和LASSO-Cox算法。
结果:我们选择了以下免疫特征基因:CCL8、PSMD1、AVPR1B和SEMG1。我们使用了射频,支持向量机,和LASSO-Cox算法。我们确定了以下免疫特征细胞:激活的肥大细胞,CD4+记忆静息T细胞,静息的肥大细胞,中性粒细胞和CD4+记忆激活的T细胞。此外,免疫特征基因和细胞的AUC值均>0.7。
结论:我们的结果表明SCZ的免疫系统功能发生了改变。此外,CCL8、PSMD1、AVPR1B和SEMG1可以调控EOS中的外周免疫细胞。Further,免疫特征基因和细胞有望成为SCZ的诊断标志物和治疗靶点。
BACKGROUND: Early-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to identify the immune characteristic genes and cells involved in EOS and to further explore the pathogenesis of EOS from the perspective of immunology.
METHODS: We obtained microarray data from a whole-genome mRNA expression in peripheral blood mononuclear cells (PBMCs); 19 patients with EOS (age range: 14.79 ± 1.90) and 18 healthy controls (HC) (age range: 15.67 ± 2.40) were involved. We screened for differentially expressed genes (DEGs) using the Limma software package and modular genes using weighted gene co-expression network analysis (WGCNA). In addition, to identify immune characteristic genes and cells, we performed enrichment analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis; we also used a random forest (RF), a support vector machine (SVM), and the LASSO-Cox algorithm.
RESULTS: We selected the following immune characteristic genes: CCL8, PSMD1, AVPR1B and SEMG1. We employed a RF, a SVM, and the LASSO-Cox algorithm. We identified the following immune characteristic cells: activated mast cells, CD4+ memory resting T cells, resting mast cells, neutrophils and CD4+ memory activated T cells. In addition, the AUC values of the immune characteristic genes and cells were all > 0.7.
CONCLUSIONS: Our results indicate that immune system function is altered in SCZ. In addition, CCL8, PSMD1, AVPR1B and SEMG1 may regulate peripheral immune cells in EOS. Further, immune characteristic genes and cells are expected to be diagnostic markers and therapeutic targets of SCZ.