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多发性硬化症患者血清 miR-191、miR-223、miR-128 和 miR-24 的时间变异性:一项 4 年随访研究。

Temporal variability of serum miR-191, miR-223, miR-128, and miR-24 in multiple sclerosis: A 4-year follow-up study.

机构信息

Neuroimmunology Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere 33520, Finland.

出版信息

J Neurol Sci. 2022 Nov 15;442:120395. doi: 10.1016/j.jns.2022.120395. Epub 2022 Aug 30.

DOI:10.1016/j.jns.2022.120395
PMID:36084364
Abstract

BACKGROUND

Circulating microRNAs (miRNA) are suggested to be a promising biomarker for multiple sclerosis (MS). Previously, miR-128-3p, miR-24-3p, miR-191-5p and miR-223-3p have been reported to associate with MS pathology. However, their longitudinal changes and association with the disease activity have not been studied.

OBJECTIVES

To evaluate the serum temporal variability of miR-128-3p, miR-191-5p, miR-24-3p, and miR-223-3p and their association with disability and disease activity in MS.

METHODS

The expression of four miRNAs in serum was studied in 57 MS patients, 18 clinically isolated syndrome patients, and 32 healthy controls over the four-year follow-up.

RESULTS

At the baseline, miR-191-5p was overexpressed in RRMS in comparison to controls, and its levels correlated positively with EDSS and progression index (PI) in RRMS. Increased levels of miR-128-3p were detected in PPMS in comparison to controls, and increased levels correlated with EDSS and PI in RRMS. The expression of miR-24-3p and miR-223-3p did not differ between the subtypes, but miR-223-3p correlated negatively with T1 lesions volumes in SPMS and PPMS. Over the four-years follow-up period, the expression of miR-128-3p and miR-24-3p was stable longitudinally, while temporal changes of miR-191-5p and miR-223-3p were observed in MS. Temporal changes in miR-191-5p were observed to be associated with an increase of EDSS or MRI activity, while the variability of miR-223-3p was associated with relapses.

CONCLUSION

Temporal variability of miR-191-5p and miR-223-3p are associated with changes in disability accumulation and disease activity. While, miR-128-3p was stably expressed and associated with the PPMS subtype and correlated with disability accumulation.

摘要

背景

循环 microRNAs(miRNA)被认为是多发性硬化症(MS)的一种很有前途的生物标志物。此前,miR-128-3p、miR-24-3p、miR-191-5p 和 miR-223-3p 已被报道与 MS 病理相关。然而,它们的纵向变化及其与疾病活动的关联尚未得到研究。

目的

评估血清 miR-128-3p、miR-191-5p、miR-24-3p 和 miR-223-3p 的时间变异性及其与 MS 患者残疾和疾病活动的相关性。

方法

在四年的随访中,对 57 例 MS 患者、18 例临床孤立综合征患者和 32 例健康对照者的血清中这四种 miRNA 的表达进行了研究。

结果

在基线时,RRMS 患者的 miR-191-5p 表达高于对照组,其水平与 RRMS 的 EDSS 和进展指数(PI)呈正相关。与对照组相比,PPMS 患者的 miR-128-3p 水平升高,与 RRMS 的 EDSS 和 PI 呈正相关。miR-24-3p 和 miR-223-3p 的表达在亚型之间没有差异,但 miR-223-3p 与 SPMS 和 PPMS 的 T1 病变体积呈负相关。在四年的随访期间,miR-128-3p 和 miR-24-3p 的表达纵向稳定,而 miR-191-5p 和 miR-223-3p 的时间变化在 MS 中观察到。miR-191-5p 的时间变化与 EDSS 或 MRI 活动的增加有关,而 miR-223-3p 的变异性与复发有关。

结论

miR-191-5p 和 miR-223-3p 的时间变异性与残疾积累和疾病活动的变化相关。而 miR-128-3p 表达稳定,与 PPMS 亚型相关,并与残疾积累相关。

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