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Micro-RNA-96 and interleukin-10 are independent biomarkers for multiple sclerosis activity

      Highlights

      • Both IL-10 and miR-96 were overexpressed during remission compared with relapse.
      • No correlation was found miR-96 expression and IL-10 levels during relapse or remission phases of MS.
      • miR-96 contributes to the remission in MS but not via IL-10 pathway.

      Abstract

      Background

      Micro-RNAs (miRNAs) are evolving as biological markers for multiple sclerosis (MS) both in activity and remission. miR-96 is associated with remission, however, the exact mechanism through which it contributes to the anti-inflammatory pathway is not clear.

      Objective

      To study the expression of miR-96 and IL-10 (anti-inflammatory mediator) in relapsing remitting (RR) MS.

      Subjects and methods

      A case control study including 32 RRMS patients from Kasr Al-Ainy MS clinic, Cairo University, Egypt, and 26 healthy controls (HC). Assessment of serum IL-10 by ELISA, and miR-96 via real time PCR was done during relapse and remission in patients, and in HC.

      Results

      IL-10 was higher in RRMS patients during remission and in HC compared with relapse (P ˂ 0.001). miR-96 expression was higher in RRMS patients during remission compared with relapse and HC, and was higher in HC than in relapse (P ˂ 0.001). IL-10 level in remission correlated positively with disease duration (r = 0.41; P = 0.02). Otherwise, no correlation was found between IL-10 and relapse number or EDSS (P>0.05). miR-96 in relapse negatively correlated with EDSS in relapse (r=−0.47; P=0.007), but no correlation was found with disease duration or relapse number, whereas, miR-96 in remission did not correlate with any clinical parameters (P>0.05). No correlation was found between IL-10 and miR-96 either in relapse or remission (P>0.05).

      Conclusion

      IL-10 and miR-96 are associated with MS quiescence, however, the lack of a significant correlation between them implicates that the influence of miR-96 may be exhibited through some pathway other than IL-10.

      Keywords

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      References

        • Compston A.
        • Coles A.
        Multiple sclerosis.
        Lancet. 2008; 372: 1502-1517
        • Stewart G.J.
        • McLeod J.G.
        • Basten A.
        • et al.
        HLA family studies and multiple sclerosis: a common gene, dominantly expressed.
        Hum. Immunol. 1981; 3: 13-29
        • Ng T.H.
        • Britton G.J.
        • Hill E.V.
        • et al.
        Regulation of adaptive immunity; the role of interleukin-10.
        Front. Immunol. 2013; 4: 129
        • Fiorentino D.F.
        • Bond M.W.
        • Mosmann T.R.
        Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.
        J. Exp. Med. 1989; 170: 2081-2095
        • Sabatos-Peyton C.A.
        • Verhagen J.
        • Wraith D.C.
        Antigen-specific immunotherapy of autoimmune and allergic diseases.
        CurrOpinImmunol. 2010; 22: 609-615
        • Tawfik T.Z.
        • Gad A.H.
        • Mehaney D.A.
        • et al.
        Interleukins 17 and 10 in a sample of Egyptian relapsing remitting multiple sclerosis patients.
        J. Neurol. Sci. 2016; 369: 36-38
        • Van Boxel-Dezaire A.H.H.
        • Hoff S.C.J.
        • Van Oosten B.W.
        • et al.
        Decreased interleukin-10 and increased interleukin-12p40 mRNA are asso- ciated with disease activity and characterize different disease stages in multiple sclerosis.
        Ann. Neurol. 1999; 45: 695-703
        • Pauley K.M.
        • Cha S.
        • Chan E.K.
        MicroRNA in autoimmunity and autoimmune disease.
        J. Autoimmun. 2009; 32: 189-194
        • Furer J.D.
        • Greenberg M.
        • Attur S.B.
        • et al.
        The role of microRNA in rheumatoid arthritis and other autoimmune diseases.
        Clin. Immunol. 2010; 136: 1-15
        • Nelson P.T.
        • Wang W.X.
        • Rajeev B.W.
        MicroRNAs (miRNAs) in neurodegenerative diseases.
        Brain Pathol. 2008; 18: 130-138
        • Otaegui D.
        • Baranzini S.E.
        • Armañanzas R.
        • et al.
        Differential microRNA expression in PBMC from multiple sclerosis patients.
        PLoSONE. 2009; 4: e6309
        • Bartel D.P.
        microRNAs: genomics, biogenesis, mechanism, and function.
        Cell. 2004; 116: 281-297
        • Bartel D.P.
        microRNAs: target recognition and regulatory functions.
        Cell. 2009; 136: 215-233
        • Liston A.
        • Linterman M.
        • Lu L.F.
        MicroRNA in the adaptive immune system, in sickness and in health.
        J ClinImmunol. 2010; 30: 339-346
        • Jeker L.T.
        • Bluestone J.A.
        Small RNA regulators of T cell-mediated autoimmunity.
        J ClinlImmunol. 2010; 30: 347-357
        • O'Connell R.M.
        • Rao D.S.
        • Chaudhuri A.A.
        • et al.
        Physiological and pathological roles for microRNAs in the immune system.
        Nat. Rev. Immunol. 2010; 10: 111-122
        • Bushati N.
        • Cohen S.M.
        MicroRNAs in neurodegeneration.
        Curr. Opin. Neurobiol. 2008; 18: 292-296
        • Yong V.W.
        Prospects of repair in multiple sclerosis.
        J. Neurol. Sci. 2009; 277: S16-S18
        • Glinsky
        SNP-guided microRNA maps (MirMaps) of 16 common human disorders identify a clinically accessible therapy reversing transcriptional aberrations of nuclear import and inflammasome pathways.
        Cell Cycle. 2008; 7: 3564-3576
        • Saunders M.A.
        • Liang H.
        • Li W.-H.
        Human polymorphism at microRNAs and microRNA target sites.
        Proc. Natl. Acad. Sci. U. S. A. 2007; 104: 3300-3305
        • Polman C.H.
        • Reingold S.C.
        • Banwell B.
        • et al.
        Diagnostic criteria for multiple sclerosis; 2010 revisions to the McDonald criteria.
        Ann. Neurol. 2011; 69: 292
        • Kurtzke J.F.
        Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).
        Neurology. 1983; 33: 1444-1452
        • Shaffer J.
        • Schlumpberger M.
        • Lader E.
        MiRNA Profiling from Blood Challenges and Recommendations.
        Qiagen Handbook, 2012: 1-10
        • Menon S.
        • Zhu F.
        • Shirani A.
        • Oger J.
        • et al.
        Disability progression in aggressive multiple sclerosis.
        Mult. Scler. J. 2017; 23: 456-463
        • Hamdy S.M.
        • Abdel-Naseer M.
        • Shalaby N.M.
        • et al.
        Characteristics and predictors of progression in an Egyptian multiple sclerosiscohort: a multicenter registry study.
        Neuropsychiatr. Dis. Treat. 2017; 13: 1895-1903
        • Heydarpour P.
        • Khoshkish S.
        • Abtahi S.
        • et al.
        Multiple sclerosis epidemiology in Middle East and North Africa: a systematic review and meta-analysis.
        Neuroepidemiology. 2015; 44: 232-244
        • El-Salem K.
        • Al-Shimmery E.
        • Horany K.
        • et al.
        Multiple sclerosis in Jordan: a clinical and epidemiological study.
        J. Neurol. 2006; 253: 1210-1216
        • Al-Araji A.
        • Mohammed A.I.
        Multiple sclerosis in Iraq: does it have the same features encountered in Western countries?.
        J. Neurol. Sci. 2005; 234: 67-71
        • Kvarnstrom M.
        • Ydrefors J.
        • Ekerfelt C.
        • et al.
        Longitudinal interferon-beta effects in multiple sclerosis: differential regulation of IL-10 and IL-17a, while no sustained effects on IFN-gamma, IL-4 or IL-13.
        J Neurol. Sci. 2013; 325: 79-85
        • Saraiva M.
        • O'Garra A.
        The regulation of IL-10 production by immune cells.
        Nat. Rev. Immunol. 2010; 10: 170-181
      1. Junker A, Krumbholz M, Eisele S, et al. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain. 2009; 1323342–3352.

        • Keller A.
        • Leidinger P.
        • Lange J.
        • et al.
        Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.
        PLoS One. 2009; 4e7440
        • Cox M.B.
        • Cairns M.J.
        • Gandhi K.S.
        • et al.
        ANZgene multiple sclerosis genetics consortium. MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood.
        PLoS One. 2010; 5e12132
      2. McCoy CE. miR-155 dysregulation and therapeutic intervention in multiple sclerosis regulation of inflammatory signaling in health and disease. In Advances in Experimental Medicine and Biology Book. Published 1967 – 2018; vol. 1024: 111–131.

        • Fenoglio C.
        • Cantoni C.
        • De Riz M.
        • et al.
        Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis.
        Neurosci. Lett. 2011; 504: 9-12
        • Regev K.
        • Healy B.C.
        • Paul A.
        • et al.
        Identification of MS-specific serum miRNAs in an international multicenter study.
        Neurol. Neuroimmunol. Neuroinflamm. 2018; 5e491