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基于多组学的偏头痛、前庭性偏头痛和梅尼埃病的免疫反应特征分析。

Multiomic-based immune response profiling in migraine, vestibular migraine and Meniere's disease.

机构信息

Meniere Disease Neuroscience Research Program, Faculty of Medicine and Health, School of Medical Sciences, The Kolling Institute, University of Sydney, Sydney, New South Wales, Australia.

Division of Otolaryngology, Department of Surgery, Instituto de Investigación Biosanitaria, ibs.GRANADA, Universidad de Granada, Granada, Spain.

出版信息

Immunology. 2024 Dec;173(4):768-779. doi: 10.1111/imm.13863. Epub 2024 Sep 18.

DOI:10.1111/imm.13863
PMID:39294737
Abstract

Migraine (MI) is the most common neurological disease, affecting with 20% of the world population. A subset of 25% of MI patients showcase concurrent vestibular symptoms, which may classify as vestibular migraine (VM). Meniere's disease (MD) is a complex inner ear disorder defined by episodes of vertigo associated with tinnitus and sensorineural hearing loss with a significant autoimmune/autoinflammatory contribution, which symptoms overlap with VM. Blood samples from 18 patients with MI (5), VM (5) and MD (8) and 6 controls were collected and compared in a case-control study. Droplet-isolated nuclei from mononuclear cells used to generate scRNAseq and scATACseq data sets from MI, VM and MD. MI and VM have no differences in their immune transcriptome; therefore, they were considered as a single cluster for further analyses. Natural Killer (NK) cells transcriptomic data support a polarisation triggered by Type 1 innate immune cells via the release of interleukin (IL)-12, IL-15 and IL-18. According to the monocyte scRNAseq data, there were two MD clusters, one inactive and one driven by monocytes. The unique pathways of the MI + VM cluster were cellular responses to metal ions, whereas MD monocyte-driven cluster pathways showed responses to biotic stimuli. MI and MD have different immune responses. These findings support that MI and VM have a Type 1 immune lymphoid cell response, and that there are two clusters of MD patients, one inactive and one Monocyte-driven.

摘要

偏头痛(MI)是最常见的神经系统疾病,影响全球 20%的人口。25%的 MI 患者出现前庭症状,可能归类为前庭性偏头痛(VM)。梅尼埃病(MD)是一种复杂的内耳疾病,其特征是眩晕发作,伴有耳鸣和感音神经性听力损失,具有显著的自身免疫/炎症反应,其症状与 VM 重叠。在一项病例对照研究中,收集了 18 名 MI(5 名)、VM(5 名)和 MD(8 名)患者和 6 名对照者的血液样本。从单核细胞中分离出的核细胞,用于生成 MI、VM 和 MD 的 scRNAseq 和 scATACseq 数据集。MI 和 VM 的免疫转录组没有差异;因此,它们被视为一个单一的聚类进行进一步分析。自然杀伤(NK)细胞转录组数据支持 1 型固有免疫细胞通过释放白细胞介素(IL)-12、IL-15 和 IL-18 触发的极化。根据单核细胞 scRNAseq 数据,有两个 MD 簇,一个不活跃,一个由单核细胞驱动。MI + VM 簇的独特途径是细胞对金属离子的反应,而 MD 单核细胞驱动的簇途径则对生物刺激有反应。MI 和 MD 具有不同的免疫反应。这些发现支持 MI 和 VM 具有 1 型免疫淋巴样细胞反应,并且 MD 患者存在两个簇,一个不活跃,一个由单核细胞驱动。

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