MicroRNA Hsa- 484 expression in Multiple sclerosis patients and its relation to radiological features

Document Type : Original Article

Authors

1 Department of Neurology, Faculty of Medicine, Minia University, Minia, Egypt

2 Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

3 Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Abstract

Abstract

Background:

Multiple sclerosis (MS) is an autoimmune disease that causes inflammatory demyelination in the central nervous system (CNS). The pathogenesis of MS involves interaction between a lot of factors including genetic, epigenetic and environmental factors. Many studies have focused on the role of micro-Ribonucleic acids in the pathogenesis of MS including miRNA 145 and miRNA 484.

Objectives:

The aim of this study is to evaluate the relation between the expression of micro-Ribonucleic acid 484 and the radiological features of MS patients.

Patients and Methods:

Plasma samples of 31 MS patients were analyzed using real time polymerase chain reaction technique to measure the relative expression of micro-Ribonucleic acid 484 in addition to MRI of those patients were analyzed for the number of T2 lesions in the brain and the spinal cord.

Results:

There was an insignificant positive correlation between miRNA expression and MRI T2 lesion number.

Conclusion:

miRNA -484 expression in MS patients is not significantly correlated with radiological features.

Highlights

Conclusion

After studying the relation between miRNA-484 expression in a group of 31 MS patients and the no of T2 lesions in the brain and spinal cord, it was found that there was upregulation of miRNA-484 expression with increased lesion number however this was insignificant.

Keywords


Introduction

Multiple sclerosis (MS) is an autoimmune disease that causes inflammatory demyeli-nation in the central nervous system (CNS). It is the leading nontrau-matic cause of neurological disability in young people.[1]

The most commonly affected sites of the CNS are periventricular white matter, brain stem, cerebellum, optic nerve and spinal cord.[2]

The main clinical characteristics of MS include relapsing remittent course of neurological symptoms, they are multiple disseminated in site and time along course of the disease. [3]

The pathogenesis of MS involves interaction between genetic, epigenetic and environmental factors. [4]

Current studies on pathophysiological changes that occur in MS have reported T-cell-mediated inflammatory responses that promotes the release of proinflammatory cytokines by immune cells, abnormalities in blood-cerebrospinal fluid (CSF) barrier permeability, macrophage activation, and the resulting progressive demyelination, also there is an increase in proinflammatory miRNAs and other pathogenic biomarkers. [5]

Definite diagnosis of MS depends on clinical assessments including neurological examination, cerebrospinal fluid (CSF) analysis, brain and spinal magnetic reso-nance imaging (MRI) and electrophysio-logical tests.[6]

Many studies have focused on the role of miRNAs in pathogenesis of MS. [7], [8]

MiRNAs are endogenous non-coding RNA that have regulatory functions. MiRNAs are formed of 21–25 nucleotides and are able to regulate mRNA expression mainly at the posttranscriptional level. [8]

Several studies have shown that miRNAs have an important role in early develop-pment and regulation of the immune system. [9]

Studies searching for microRNA 484 expression in MS patients showed that there was significant upregulation of its expression in MS patients vs control group. [10], [11]

Aim of the study

The aim of the study to evaluate miRNA 484 expression in MS patients and correlation with MRI T2 lesion load.

Methods

The study included 31 MS patients with no other neurological or autoimmune comor-bidities.

Patients are diagnosed to have MS using Mc Donald criteria 2017.

Brain and spinal cord T 2 lesions were analyzed by 1.5 tesla MRI device.

Brain T2 lesion number is categorized to three groups: lesion number from 0- 5, from 5-10, more than 10 lesions respectively.

plasma samples of MS patients were analyzed for miRNA-484 expression by real time quantitative polymerase chain reaction (PCR) after miRNA extraction using miRNeasy supplied by Qiagen.

Statistical analysis

The collected data was analyzed using Statistical Package for Social Science (SPSS 20).

A 2-sided probability (P) value was used for all statistical analyses and a P value of <0.05 was considered statistically signifi-cant.

Correlation between miRNA expression and MRI T2 lesion no in brain and spinal cord using Kruskal Wallis test.

Results

It was found that microRNA expression increases with the increase of T2 brain and spine lesion number, however this is statistically insignificant. (P-value = 0.89), (P-value = 0.62) respectively (table 1), (table 2), (figure 1)

Discussion

Magnetic resonance imaging analysis of lesions help in defining the pathobiology reflected by biomarkers. Since miRNAs regulate several cellular pathways included in pathogenesis of MS, it is hypothesized that different miRNAs expressions may show relations with specific MRI measures of brain and spinal cord lesions.

Several studies searched for the relation between miRNAs expression and MRI lesions.

Regev et al., found that four miRNAs showed significant protective correlations with T1:T2 lesion volume, with the others included hsa.miR.486.5p and hsa.miR.92a.3p showed significant pathogenic correlations with T1:T2 and hsa.miR.375 showed significant patho-genic correlations with brain atrophy. [12]

Also, they found significant pathogenic relation between hsa.miRNA.484 and whole brain volume as well as central gray matter volume.

  1. References

    1. Nicholas and W. Rashid, “Multiple sclerosis,” Am. Fam. Physician, vol. 87, no. 10, pp. 712–714, 2013.
    2. Katsara and V. Apostolopoulos, “Editorial: Multiple Sclerosis: Patho-genesis and Therapeutics,” Med. Chem. (Los. Angeles)., vol. 14, no. 2, pp. 104–105, 2018, doi: 10.2174/ 157340641402180206092504.
    3. Cappelle et al., “A validation study of manual atrophy measures in patients with Multiple Sclerosis,” Neuroradio-logy, vol. 62, no. 8, pp. 955–964, 2020, doi: 10.1007/s00234-020-02401-3.
    4. Wasser et al., “CNS-localized myeloid cells capture living invading T cells during neuroinflammation,” J. Exp. Med., vol. 217, no. 6, 2020, doi: 10.1084/jem.20190812.
    5. Akaishi, T. Takahashi, and I. Nakashima, “Oligoclonal bands and periventricular lesions in multiple sclerosis will not increase blood-brain barrier permeability,” J. Neurol. Sci., vol. 387, no. November 2017, pp. 129–133, 2018, doi: 10.1016/j.jns. 2018. 02.020.
    6. D. Lublin et al., “,” Neurology, 2014.
    7. Zhou et al., “Genetic variation within miR-146a predicts disease onset & relapse in multiple sclerosis,” Mult. Scler., vol. 23, no. 11 Suppl., pp. 79–80, 2018.
    8. Yang, W. Pan, and L. Qian, “Identification of the miRNA–mRNA regulatory network in multiple sclerosis,” Neurol. Res., vol. 39, no. 2, pp. 142–151, 2017, doi: 10.1080/ 01616412.2016.1250857.
    9. Essandoh, Y. Li, J. Huo, and G.-C. Fan, “MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response.,” Shock, vol. 26, no. 2, pp. 122–131, 2016, doi: https://doi.org/ 10.1097/SHK.0000000000000604.
    10. B. Søndergaard, D. Hesse, M. Krakauer, P. S. Sørensen, and F. Sellebjerg, “Differential microRNA expression in blood in multiple sclerosis,” Mult. Scler. J., vol. 19, no. 14, pp. 1849–1857, 2013, doi: 10.1177/ 1352458513490542.
    11. Keller et al., “Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls,” PLoS One, vol. 4, no. 10, 2009, doi: 10.1371/journal. pone.0007440.
    12. Regev et al., “Association between serum MicroRNAs and magnetic resonance imaging measures of multiple sclerosis severity,” JAMA Neurol., vol. 74, no. 3, pp. 275–285, 2017, doi: 10.1001/jamaneurol.2016. 5197.