Cytokine profiling and transcriptomics in mononuclear cells define immune variants in Meniere Disease

IF 5 3区 医学 Q1 GENETICS & HEREDITY Genes and immunity Pub Date : 2024-02-23 DOI:10.1038/s41435-024-00260-z
Marisa Flook, Elena Rojano, Alvaro Gallego-Martinez, Alba Escalera-Balsera, Patricia Perez-Carpena, M. del Carmen Moleon, Rocio Gonzalez-Aguado, Victoria Rivero de Jesus, Emilio Domínguez-Durán, Lidia Frejo, Juan A. G. Ranea, Jose Antonio Lopez-Escamez
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Abstract

Meniere Disease (MD) is a chronic inner ear disorder characterized by vertigo attacks, sensorineural hearing loss, tinnitus, and aural fullness. Extensive evidence supporting the inflammatory etiology of MD has been found, therefore, by using transcriptome analysis, we aim to describe the inflammatory variants of MD. We performed Bulk RNAseq on 45 patients with definite MD and 15 healthy controls. MD patients were classified according to their basal levels of IL-1β into 2 groups: high and low. Differentially expression analysis was performed using the ExpHunter Suite, and cell type proportion was evaluated using the estimation algorithms xCell, ABIS, and CIBERSORTx. MD patients showed 15 differentially expressed genes (DEG) compared to controls. The top DEGs include IGHG1 (p = 1.64  $$\times$$  10−6) and IGLV3-21 (p = 6.28  $$\times$$  10−3), supporting a role in the adaptative immune response. Cytokine profiling defines a subgroup of patients with high levels of IL-1β with up-regulation of IL6 (p = 7.65  $$\times$$  10−8) and INHBA (p = 3.39  $$\times$$  10−7) genes. Transcriptomic data from peripheral blood mononuclear cells support a proinflammatory subgroup of MD patients with high levels of IL6 and an increase in naïve B-cells, and memory CD8+ T cells.

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单核细胞中的细胞因子分析和转录组学确定了梅尼埃病的免疫变异。
梅尼埃病(MD)是一种慢性内耳疾病,以眩晕发作、感音神经性听力损失、耳鸣和耳部饱胀为特征。已有大量证据支持梅尼埃病的炎症病因,因此,我们希望通过转录组分析来描述梅尼埃病的炎症变异。我们对 45 名明确的 MD 患者和 15 名健康对照者进行了大容量 RNAseq 分析。根据 IL-1β 的基础水平将 MD 患者分为两组:高组和低组。使用 ExpHunter 套件进行了差异表达分析,并使用 xCell、ABIS 和 CIBERSORTx 估算算法评估了细胞类型比例。与对照组相比,MD 患者有 15 个差异表达基因(DEG)。最主要的差异表达基因包括 IGHG1(p = 1.64 [公式:见正文] 10-6)和 IGLV3-21(p = 6.28 [公式:见正文] 10-3),支持在适应性免疫反应中发挥作用。细胞因子图谱确定了一个高水平 IL-1β 的患者亚群,其中 IL6(p = 7.65 [公式:见正文] 10-8)和 INHBA(p = 3.39 [公式:见正文] 10-7)基因上调。来自外周血单核细胞的转录组数据证实,MD 患者中存在一个促炎症亚组,其 IL6 水平较高,幼稚 B 细胞和记忆 CD8+ T 细胞增多。
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来源期刊
Genes and immunity
Genes and immunity 医学-免疫学
CiteScore
8.90
自引率
4.00%
发文量
28
审稿时长
6-12 weeks
期刊介绍: Genes & Immunity emphasizes studies investigating how genetic, genomic and functional variations affect immune cells and the immune system, and associated processes in the regulation of health and disease. It further highlights articles on the transcriptional and posttranslational control of gene products involved in signaling pathways regulating immune cells, and protective and destructive immune responses.
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