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典型和非标准型产科抗磷脂综合征(OAPS和NC - OAPS)患者差异基因表达及免疫和炎症反应机制的转录组学分析

Transcriptomics analysis of differential gene expression and immune and inflammatory response mechanisms in patients with typical and non-criteria obstetric antiphospholipid syndrome (OAPS and NC-OAPS).

作者信息

Qi Xuan, Liu Peng, Zhou Yingjie, Lei Lingyan, Xue Guoyu, Wang Ronghua, Wang Junping, Guo Huifang

机构信息

Department of Rheumatism and Immunology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.

Department of Laboratory, Hebei Provincial Reproductive Health Hospital, Shijiazhuang, Hebei 050000, PR China.

出版信息

J Reprod Immunol. 2024 Dec;166:104389. doi: 10.1016/j.jri.2024.104389. Epub 2024 Nov 7.

DOI:10.1016/j.jri.2024.104389
PMID:39522423
Abstract

In this study, we investigated the molecular differences between patients with typical obstetric antiphospholipid syndrome (OAPS) and patients with non-criteria obstetric antiphospholipid syndrome (NC-OAPS) patients through transcriptome sequencing of peripheral blood samples from ten OAPS patients and ten NC-OAPS patients. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, protein-protein interaction (PPI) analysis, and competitive endogenous RNA (ceRNA) network construction to identify hub genes. Verification was performed via Quantitative Real-time PCR (qPCR) in OAPS (n=9) and NC-OAPS (n=12) samples. We identified 240 DEGs in two groups. GO and KEGG analyses reviewed upregulated in pathways related to the inflammatory response; immune response; antigen processing and presentation; Th1, Th2, and Th17 cell differentiation; and NK cell-mediated cytotoxicity in OAPS patients. PPI and ceRNA network analyses identified key genes, with significant upregulation of CXCR2, JAK2, and MPO found in the OAPS group, which correlated with severe inflammation, JAK-STAT pathway activation, and increased NET activity in neutrophils. Other genes such as CD4, IL2RB, and NKG7, are involved in T-cell and NK cell regulation. Our results indicate enhanced inflammatory and immune responses in OAPS patients, suggesting more severe immune activity than in NC-OAPS patients, providing a basis for precise diagnostic and therapeutic strategies.

摘要

在本研究中,我们通过对10例典型产科抗磷脂综合征(OAPS)患者和10例非标准产科抗磷脂综合征(NC - OAPS)患者的外周血样本进行转录组测序,研究了这两组患者之间的分子差异。我们鉴定了差异表达基因(DEG),随后进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析、蛋白质 - 蛋白质相互作用(PPI)分析以及竞争性内源性RNA(ceRNA)网络构建以识别枢纽基因。通过定量实时PCR(qPCR)在OAPS(n = 9)和NC - OAPS(n = 12)样本中进行验证。我们在两组中鉴定出240个DEG。GO和KEGG分析显示,OAPS患者中与炎症反应、免疫反应、抗原加工和呈递、Th1、Th2和Th17细胞分化以及NK细胞介导的细胞毒性相关的通路上调。PPI和ceRNA网络分析确定了关键基因,在OAPS组中发现CXCR2、JAK2和MPO显著上调,并与严重炎症、JAK - STAT通路激活以及中性粒细胞中NET活性增加相关。其他基因如CD4、IL2RB和NKG7参与T细胞和NK细胞调节。我们的结果表明OAPS患者的炎症和免疫反应增强,提示其免疫活性比NC - OAPS患者更严重,为精确的诊断和治疗策略提供了依据。

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