الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
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Abstract
Multiple sclerosis (MS) is the most common disabling neurologic disease among young adults. Etiologically, MS is a multifactorial disease in which both genetic and environmental factors contribute to disease progression. The HLA-DRB1*15:01 allele is the most strongly linked genetic risk factor for MS (Romero-Pinel et al., 2011). Up to date, no laboratory test or test set can guarantee MS diagnosis. Early therapeutic intervention is highly recommended, highlighting the crucial importance of rapid and accurate disease diagnosis. miRNA dysregulation has been found to be associated with almost all disease conditions. Coupled with the stability of extracellular miRNAs and simplicity of their detection, circulating miRNAs have been positioned as promising biomarkers for various human diseases including MS (Gilad et al., 2008). miRNAs would contribute for improved MS diagnosis as well as for monitoring disease activity and treatment response.
The current study aimed at characterization of the expression levels of serum miR-145, miR-223 and miR-326 in patients with MS as well as in patients with other neuroinflammatory disorders and to investigate their clinical relevance for early and differential diagnosis of MS. The study also involved the analysis of the expression levels of certain target genes in peripheral blood leukocytes (PBLs) to evaluate their possible contribution to MS pathogenesis. In addition, genotyping of HLA-DRB1*15:01 was investigated to denote for its association with MS in Egyptian patients.
A total of 80 subjects were enrolled in the present study, including 37 patients with MS (relapsing-remitting MS [RRMS; n=18] and secondary progressive MS [SPMS; n=19]) and 20 patients with other clinically related diseases (neuromyelitis optica spectrum disorder [NMOSD; n=10] and neuropsychiatric systemic lupus erythematosus [NPSLE; n=10]) as well as 23 healthy volunteers serving as control subjects. Serum expression levels of three selected miRNAs (miR-145, miR-223 and miR-326) were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Whole blood expression levels of two cellular immune response-associated target genes (signaling mother against decapentaplegic peptide 3 [SMAD3] and specificity protein 1 [SP1]) were also measured using qRT-PCR. In addition, genotyping of the DRB1*15:01 allele was carried out using restriction fragment length polymorphism (RFLP)-PCR.
The DRB1*15:01 allele frequency was very low suggesting its less informativeness in the Egyptian patients. The three miRNAs were upregulated in MS and NMOSD patients, whereas only miR-145 and miR-223 revealed significant upregulation in MS. On the other hand, the examined miRNAs were significantly down-regulated in NPSLE. To analyze the discriminatory power of each miRNA, receiver operator characteristic curves (ROC) were computed and a subsequent stepwise combined analysis was performed to evaluate whether a composite of any of these miRNAs may have higher differentiation potential. The three miRNAs showed highly diagnostic potential for distinguishing MS from NPSLE. Their combined use would also be useful for discriminating between MS and NMOSD as well as RRMS and SPMS. Besides, the expression levels of SMAD3 and SP1were decreased in MS and NMOSD patients. In NPSLE patients, SMAD3 was down-expressed and SP1 was slightly over-expressed. The significant dysregulation was only reported for SP1 and SMAD3 in MS and NPSLE, respectively.
In conclusion, miR-145, miR-223 and miR-326 expression profile would provide considerable potential for differentiating between MS and NPSLE, and to a lesser extent between MS and NMOSD as well as RRMS and SPMS. Despite the preliminary character of our study, our results provide a rationale for validation in larger case-control cohorts.