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在单核细胞中进行细胞因子分析和转录组学分析可定义梅尼埃病的免疫变异。

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

机构信息

Otology and Neurotology Group CTS495, Division of Otolaryngology, Department of Surgery, Instituto de Investigación Biosanitaria, ibs.GRANADA, Granada, Universidad de Granada, Granada, Spain.

Sensorineural Pathology Programme, Centro de Investigación Biomédica en Red en Enfermedades Raras, CIBERER, Madrid, Spain.

出版信息

Genes Immun. 2024 Apr;25(2):124-131. doi: 10.1038/s41435-024-00260-z. Epub 2024 Feb 23.

DOI:10.1038/s41435-024-00260-z
PMID:38396174
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11023934/
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   10) and IGLV3-21 (p = 6.28   10), 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   10) and INHBA (p = 3.39   10) 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.

摘要

梅尼埃病(MD)是一种慢性内耳疾病,其特征是眩晕发作、感音神经性听力损失、耳鸣和耳闷。大量证据支持 MD 的炎症病因,因此,我们通过使用转录组分析,旨在描述 MD 的炎症变异。我们对 45 例明确的 MD 患者和 15 例健康对照进行了 Bulk RNAseq。根据患者的基础 IL-1β 水平,将 MD 患者分为高和低 2 组。使用 ExpHunter Suite 进行差异表达分析,并使用 xCell、ABIS 和 CIBERSORTx 评估细胞类型比例。与对照组相比,MD 患者显示出 15 个差异表达基因(DEG)。顶级 DEGs 包括 IGHG1(p=1.64×10)和 IGLV3-21(p=6.28×10),支持在适应性免疫反应中发挥作用。细胞因子谱定义了一组具有高水平 IL-1β 的患者亚组,其中 IL6(p=7.65×10)和 INHBA(p=3.39×10)基因上调。来自外周血单核细胞的转录组数据支持 MD 患者中存在高水平 IL6 的促炎亚组,并伴有幼稚 B 细胞和记忆 CD8 T 细胞增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/11023934/743b97b227ce/41435_2024_260_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/11023934/7613ca8e99a2/41435_2024_260_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/11023934/743b97b227ce/41435_2024_260_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/11023934/7613ca8e99a2/41435_2024_260_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5450/11023934/743b97b227ce/41435_2024_260_Fig2_HTML.jpg

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Otolaryngol Head Neck Surg. 2023 Nov;169(5):1122-1131. doi: 10.1002/ohn.386. Epub 2023 Jun 5.
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Serum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model.
J Mol Med (Berl). 2025 Aug 6. doi: 10.1007/s00109-025-02581-6.
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Optimizing staging of Meniere's disease: integrating electrocochleography with vestibular tests.优化梅尼埃病的分期:将耳蜗电图与前庭测试相结合。
Front Neurosci. 2025 Jul 8;19:1600665. doi: 10.3389/fnins.2025.1600665. eCollection 2025.
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An ultra-rare missense variant in the KIF1B gene linked to autoinflammatory Menière's disease.KIF1B基因中的一种超罕见错义变体与自身炎症性梅尼埃病相关。
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Preclinical Models to Study the Molecular Pathophysiology of Meniere's Disease: A Pathway to Gene Therapy.用于研究梅尼埃病分子病理生理学的临床前模型:基因治疗的途径
J Clin Med. 2025 Feb 20;14(5):1427. doi: 10.3390/jcm14051427.
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