Abstract
It is well established that Multiple Sclerosis (MS) is an immune mediated disease. Little is known about what drives the differential control of the immune system in MS patients compared to unaffected individuals. MicroRNAs (miRNAs) are small non-coding nucleic acids that are involved in the control of gene expression. Their potential role in T cell activation and neurodegenerative disease has recently been recognised and they are therefore excellent candidates for further studies in MS. We investigated the transcriptome of currently known miRNAs using miRNA microarray analysis in peripheral blood samples of 59 treatment naïve MS patients and 37 controls. Of these 59, 18 had a primary progressive, 17 a secondary progressive and 24 a relapsing remitting disease course. In all MS subtypes miR-17 and miR-20a were significantly under-expressed in MS, confirmed by RT-PCR. We demonstrate that these miRNAs modulate T cell activation genes in a knock-in and knock-down T cell model. The same T cell activation genes are also up-regulated in MS whole blood mRNA, suggesting these miRNAs or their analogues may provide useful targets for new therapeutic approaches.
Highlights
Multiple Sclerosis (MS) is a disease which affects mainly young people that often leaves them disabled in their most productive years
There was no significant difference in the demographics between the group assessed by microarray and the one assessed by RT-PCR
As expected the disease duration and the expanded disability status scale (EDSS) was higher in the SP and PP group compared to the RR group
Summary
Multiple Sclerosis (MS) is a disease which affects mainly young people that often leaves them disabled in their most productive years. It is a relatively common disease with an incidence somewhere between 1–2 per 1000 and the rate appears to be increasing [1]. Most patients have a relapsing remitting course (RRMS), which is unpredictable and is observed as episodes of acute inflammation that results in neurological dysfunction, which in the majority of cases responds to immunomodulatory steroid treatment. Relapsing remitting disease is characterized by some level of myelin repair, whereas in the progressive form myelin repair seems to be insufficient or ineffectual resulting in progressive disability without any observable signs of recovery. In recent years genome wide association studies have identified that is there an association with haplotype in the Human Leukocyte Antigen (HLA) region, and in both the IL-2 and the IL-7 receptor genes, CD56, CD226 and CLEC16A, which together are considered to contribute to a predisposition to develop the disease [3,4,5]
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