الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Multiple sclerosis (MS) is a chronic multifocal inflammatory demyelinating disease with progressive neurodegeneration caused by an autoimmune response to self-antigens in an individual who is genetically susceptible. Clinical symptoms vary depending on the site of neurologic lesions and correlate with the invasion of inflammatory cells across the blood-brain barrier (BBB) result in demyelination and edema.
The immunopathogenesis of multiple sclerosis is considered as a complicated picture that needs to be elucidated. The factors that initiate inflammation are still unknown, but it is believed that MS is caused by environmental factors in the host that has genetic susceptibility which trigger a T-cell autoimmune response against the CNS.
Primarily it was supposed that a subset of T helper 1 (Th1) which produce interferon γ (IFN-γ) is critical in autoimmunity of MS, however it is now clear that Th17, are the main responsible cells for inflammation and pathogenesis of MS.
MS is a very complicated disease and even magnetic resonance imaging (MRI), as a preferred diagnostic method, does not correlate with the disease severity, progression and response to treatment. Therefore, there is a great need for new and more specific biomarkers, which could elucidate pathology as well as provide prognosis of disease and therapeutic response in MS patients
In recent years several studies are conducted on the presence and the role of miRNA in MS, suggesting that there are varieties of pathways regulated by miRNA. MiRNAs are a class of endogenous small, non-coding RNAs of average 22 nucleotide long, that regulate gene expression at the post-transcriptional level results in translational repression or mRNA degradation leading to a decrease in encoded protein.
In this study, we aimed to detect the expression of miR-26a in peripheral blood mononuclear cells (PBMCs) of relapsing–remitting MS (RRMS) patients during relapsing and remitting phases compared to healthy control subjects and correlate this expression to the level of serum IL17.
This study was conducted on 40 patients who are diagnosed as definite multiple sclerosis cases according to MacDonald criteria (relapsing remitting type) and admitted to multiple sclerosis unit at Ain Shams University Hospital with a mean age of (27.75 ±4.21) and 20 healthy control subjects with a mean age of (25.15 ± 2.78) in the period from February 2016 to October 2016.
Five ml blood samples were collected from all the participants under complete standard aseptic technique, as 3 ml in EDTA tube for qRT-PCR to detect miR26a and 2 ml blood in a tube without additives for ELISA to detect serum IL 17.
The results of present study showed that there was a statistically significant difference between patients and control groups regarding miR26a relative expression levels (P<0.001) and serum IL17 level (P<0.001).
Also, a statistically significant difference was observed between remitting MS patients and control groups regarding miR26a relative expression levels (P <0.001) and serum IL17 level (P <0.001).
Comparison between relapsing MS patients and control groups showed a statistically significant difference regarding miR26a relative expression levels (P 0.004) but there was a statistically insignificant difference between both groups regarding serum IL17 level.
Also, there was statistically insignificant correlation between miR26a versus IL17 in all MS patients.
We correlated miR26a and IL17 with duration of disease, and EDSS as patient clinical parameters in relapsing and remitting patients. We observed that in both relapsing and remitting patients, there was statistically insignificant correlation between miR26a and duration of disease & EDSS.
As regarding IL17, the only statistically significant correlation was the inverse correlation between IL17 and duration of the disease among relapsing MS patients. This was explained as Th17 immune response could be more important for MS onset rather than further disease development and progression.
Conclusion:
• The current study reported up-regulation of miR-26a and IL-17 in peripheral blood mononuclear cells (PBMCs) in all MS patients (including remitting and relapsing patients) in comparison with healthy subjects. This may suggest use of both miR26a and IL17 as potential biomarkers for understanding pathogenesis of MS disease and the capacity of miR26a to modulate Th17 differentiation, as postulated by many other studies, makes both of them as two therapeutic targets for prevention of MS disease progression.
• Use of miR-26a and IL-17 as diagnostic biomarker would be incredibly valuable due to difficulties and challenges in collecting other target tissues (CSF, brain tissue) from multiple sclerosis patients, while peripheral blood is more convenient to obtain.
• This study proposed that miR-26a and IL-17, as two diagnostic biomarkers, could be used not only for detection of RRMS patients but also for evaluation of the effectiveness of drug therapy in patients with RRMS. Meanwhile, they could be identified as two therapeutic targets for prevention of MS disease progress.