Abstract
Multiple sclerosis (MS) is a debilitating autoimmune disease affecting over 2.3 million people worldwide, and it is characterized by inflammation and demyelination of nerve cells. The currently available biomarkers for the diagnosis and management of MS have inherent limitations, therefore, additional new biomarkers are needed. We studied the microRNA (miRNA) profile of splenocytes of mice having experimental autoimmune encephalomyelitis (EAE), a model of human MS. A miRNA-microarray analysis revealed increased expression of nine miRNAs (let-7e, miR-23b, miR-31, miR-99b, miR-125a, miR-146b, miR-155, miR-193b, and miR-221) following EAE development. Interestingly, serum levels of miR-99b, miR-125a, and miR-146b were significantly higher in EAE mice compared to normal mice. Bioinformatics analysis revealed the experimentally validated as well as predicted gene targets of specific miRNAs that are important for disease progression in MS. Specifically, we observed inverse correlation in the levels of miR-99b versus LIF, and between miR-125a versus BDNF and LIF. Our results suggest that above-mentioned miRNAs may play a crucial role in the pathogenesis of MS, and that miR-99b, miR-125a, and miR-146b in particular may serve as useful biomarkers for disease activity.
Highlights
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) and it is characterized by inflammation and demyelination of neurons
There are three main tests used to aid the clinical diagnosis and management of MS [11], namely the oligoclonal bands in the cerebrospinal fluid (CSF) [12], which are attributable mostly to immunoglobulins; the white matter/Gadolinium (Gad)-enhancing lesions detected by magnetic resonance imaging (MRI) [13,14], which correspond to active lesions with inflammation; and the John Cunningham (JC) virus antibody titers [15,16], which demonstrate exposure of the patient to this virus and the likely risk of developing progressive multifocal leukoencephalopathy (PML) following immunosuppressive therapy
RNA was isolated from SPCs of EAE and control mice, and cultured in medium alone or medium containing MOG35–55
Summary
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) and it is characterized by inflammation and demyelination of neurons. There are three main tests used to aid the clinical diagnosis and management of MS [11], namely the oligoclonal bands in the cerebrospinal fluid (CSF) [12], which are attributable mostly to immunoglobulins; the white matter/Gadolinium (Gad)-enhancing lesions detected by magnetic resonance imaging (MRI) [13,14], which correspond to active lesions with inflammation; and the John Cunningham (JC) virus antibody titers [15,16], which demonstrate exposure of the patient to this virus and the likely risk of developing progressive multifocal leukoencephalopathy (PML) following immunosuppressive therapy. We believe that microRNAs (miRNAs) can fill this gap and reinforce the existing tests for MS
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