Differential Expression of Serum Extracellular Vesicle miRNAs in Multiple Sclerosis: Disease-Stage Specificity and Relevance to Pathophysiology

International Journal of Molecular Sciences

Markus Otto¹  André Huss²  Hayrettin Tumani²  Giancarlo Russo³  Roland Martin⁴  Nagiua Cuomo-Haymour⁵  Giorgio Bergamini⁵  Christopher R. Pryce⁵  Irene Knuesel⁶  Luka Kulic⁶ 

[1] Department of Neurology, University Hospital Halle, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany;Department of Neurology, University Hospital Ulm, 89081 Ulm, Germany;Functional Genomics Centre Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, 8057 Zurich, Switzerland;Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, 8006 Zurich, Switzerland;Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, 8008 Zurich, Switzerland;Roche Innovation Center Basel, Neuroimmunology Division, Roche Pharma Research and Early Development, 4070 Basel, Switzerland;

关键词: clinically isolated syndrome;    relapsing–remitting multiple sclerosis;    inflammation;    extracellular vesicles;    microRNA;    biomarker;   

DOI  :  10.3390/ijms23031664

来源: DOAJ

【 摘 要 】

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) is often followed by the development of relapsing–remitting MS (RRMS). The periphery-to-CNS transmission of inflammatory molecules is a major pathophysiological pathway in MS. This could include signalling via extracellular vesicle (EV) microRNAs (miRNAs). In this study, we investigated the serum EV miRNome in CIS and RRMS patients and matched controls, with the aims to identify MS stage-specific differentially expressed miRNAs and investigate their biomarker potential and pathophysiological relevance. miRNA sequencing was conducted on serum EVs from CIS-remission, RRMS-relapse, and viral inflammatory CNS disorder patients, as well as from healthy and hospitalized controls. Differential expression analysis was conducted, followed by predictive power and target-pathway analysis. A moderate number of dysregulated serum EV miRNAs were identified in CIS-remission and RRMS-relapse patients, especially relative to healthy controls. Some of these miRNAs were also differentially expressed between the two MS stages and had biomarker potential for patient-control and CIS–RRMS separations. For the mRNA targets of the RRMS-relapse-specific EV miRNAs, biological processes inherent to MS pathophysiology were identified using in silico analysis. Study findings demonstrate that specific serum EV miRNAs have MS stage-specific biomarker potential and contribute to the identification of potential targets for novel, efficacious therapies.

【 授权许可】

Unknown