miR-155 and functional proteins of CD8+T cells as potential prognostic biomarkers for relapsing-remitting multiple sclerosis

被引:10
作者
Elkhodiry, Aya A. [1 ]
Zamzam, Dina A. [2 ]
El Tayebi, Hend M. [1 ]
机构
[1] German Univ Cairo, Fac Pharm & Biotechnol, Dept Pharmacol Toxicol & Clin Pharm, Mol Pharmacol Res Grp, Cairo, Egypt
[2] Ain Shams Univ, Fac Med, Dept Neurol, Cairo, Egypt
关键词
Multiple Sclerosis; miR-155; EDSS; Biomarkers; CD8+T cells; GENE-EXPRESSION; T-CELLS; MIRNA EXPRESSION; MICRORNAS; INFILTRATE; LESIONS;
D O I
10.1016/j.msard.2021.103078
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that results in neurological deficits in patients leading to disabilities which are evaluated on a scale known as the Expanded Disability Status Scale (EDSS). The most prevalent subtype of the disease is Relapsing-Remitting Multiple sclerosis (RRMS). One of the key players in MS pathogenesis is CD8+ T cells present in abundance in MS lesions expressing surface receptors, intracellular adhesion molecule (ICAM1) and integrin Subunit Beta 2 (ITGB2). These proteins are crucial for migration through the blood-brain barrier (BBB) and secondary stimulatory signal, along with the cytotoxic proteins perforin and granzymeB that attack oligodendrocytes. MicroRNAs (miRNAs) are small non-coding RNAs that play a substantial regulatory role in various disease pathogeneses through post-transcriptional modifications, and miR-155 shows potential for its use as a biomarker of the disease. The study aims at investigating the expression of miR-155, ICAM1, ITGB2, perforin and GranzymeB in CD8+ T cells of RRMS patients receiving different treatment regimens and how these genes correlate with patients' EDSS and miR-155 expression. Methods: Gene expression of miR-155, ICAM1, ITGB2, perforin and granzymeB was evaluated using RT-qPCR in CD8+ T cells isolated from blood samples of RRMS patients and compared to healthy controls. Results: Results showed downregulation of miR-155 and upregulation of surface receptors and cytotoxic proteins in CD8+T cells with significant correlation with each other and patients' EDSS. Conclusion: This study helps pave the road for the discussed genes for their use as potential biomarkers of disease disability and future investigations on their regulatory roles in disease pathogenesis.
引用
收藏
页数:8
相关论文
共 43 条
[1]   Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis [J].
Axelsson, M. ;
Malmestrom, C. ;
Nilsson, S. ;
Haghighi, S. ;
Rosengren, L. ;
Lycke, J. .
JOURNAL OF NEUROLOGY, 2011, 258 (05) :882-888
[2]   Clonal expansions of CD8+ T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction [J].
Babbe, H ;
Roers, A ;
Waisman, A ;
Lassmann, H ;
Goebels, N ;
Hohlfeld, R ;
Friese, M ;
Schröder, R ;
Deckert, M ;
Schmidt, S ;
Ravid, R ;
Rajewsky, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (03) :393-404
[3]   Immune-related miRNA expression patterns in peripheral blood mononuclear cells differ in multiple sclerosis relapse and remission [J].
Baulina, Natalia ;
Kulakova, Olga ;
Kiselev, Ivan ;
Osmak, German ;
Popova, Ekaterina ;
Boyko, Alexey ;
Favorova, Olga .
JOURNAL OF NEUROIMMUNOLOGY, 2018, 317 :67-76
[4]   Multiple sclerosis: Etiology, symptoms, incidence and prevalence, and implications for community living and employment [J].
Bishop, Malachy ;
Rumrill, Phillip D. .
WORK-A JOURNAL OF PREVENTION ASSESSMENT & REHABILITATION, 2015, 52 (04) :725-734
[5]   A roadmap to precision medicine for multiple sclerosis [J].
Chitnis, Tanuja ;
Prat, Alexandre .
MULTIPLE SCLEROSIS JOURNAL, 2020, 26 (05) :522-532
[6]   Personalized medicine in multiple sclerosis: hope or reality? [J].
Derfuss, Tobias .
BMC MEDICINE, 2012, 10
[7]   Adhesion molecules in multiple sclerosis -: Relation to subtypes of disease methylprednisolone therapy [J].
Elovaara, I ;
Ukkonen, M ;
Leppäkynnäs, M ;
Lehtimäki, T ;
Luomala, M ;
Peltola, J ;
Dastidar, P .
ARCHIVES OF NEUROLOGY, 2000, 57 (04) :546-551
[8]   Non-coding RNAs in human disease [J].
Esteller, Manel .
NATURE REVIEWS GENETICS, 2011, 12 (12) :861-874
[9]   Altered T cell phenotypes associated with clinical relapse of multiple sclerosis patients receiving fingolimod therapy [J].
Fujii, Chihiro ;
Kondo, Takayuki ;
Ochi, Hirofumi ;
Okada, Yoichiro ;
Hashi, Yuichiro ;
Adachi, Tetsuya ;
Shin-Ya, Masaharu ;
Matsumoto, Sadayuki ;
Takahashi, Ryosuke ;
Nakagawa, Masanori ;
Mizuno, Toshiki .
SCIENTIFIC REPORTS, 2016, 6
[10]   Circulating CD8+CD56-perforin+ T cells are increased in multiple sclerosis patients [J].
Giovanni, Frisullo ;
Domenico, Plantone ;
Alessandro, Marti ;
Raffaele, Iorio ;
Viviana, Nociti ;
Katia, Patanella Agata ;
Paola, Batocchi Anna .
JOURNAL OF NEUROIMMUNOLOGY, 2011, 240 :137-141