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纤维肌痛症患者免疫细胞中转座元件的激活。

Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients.

机构信息

School of Medicine, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain.

Université de Poitiers, CEDEX, 86073 Poitiers, France.

出版信息

Int J Mol Sci. 2020 Feb 18;21(4):1366. doi: 10.3390/ijms21041366.

Abstract

Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS. The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.

摘要

核酸测序技术的进步以及元数据的空前可用性揭示,人类基因组中由转座元件 (TEs) 构成的 45%不仅具有转录活性,而且在生理上也是必需的。转座元件的失调,包括人类逆转录病毒内源性序列 (HERVs),与几种神经和自身免疫性疾病有关,包括肌痛性脑脊髓炎/慢性疲劳综合征 (ME/CFS)。然而,尚无研究表明这些序列的异常表达是否与纤维肌痛 (FM) 相关,纤维肌痛常与 ME/CFS 合并存在。本研究首次表明,实际上,HERV 的 H、K 和 W 型在有或没有合并 ME/CFS 的 FM 患者的免疫细胞中过度表达。HERV 表达增加的患者 (N=14) 表现出干扰素 (INF-β 和 INF-γ) 水平升高,但 TNF-α 水平不变。本研究报告的发现可以解释临床上 FM 患者出现的流感样症状,而不存在合并感染。有必要开展进一步的研究,以确定在 FM 和/或 ME/CFS 中受到差异影响的特定基因组位点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0e3/7072917/2e590ab87a95/ijms-21-01366-g001.jpg

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