الفهرس 
MULTIPLE SCLEROSISOnly 14 pages are availabe for public view
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Abstract
ultiple sclerosis is a chronic autoimmune disease of the central nervous system in which inflammation, demyelination, and axonal loss occurs in early stages of the disease. Egypt has got the highest number of MS patients in the Middle East region with estimated number of 59,671 subjects. Impaired mitochondrial function has been implicated in the pathogenicity of MS. Damage to mitochondrial DNA (mtDNA) can cause alteration in the copy number (CN) and decline in mitochondrial function.
Our aim was to evaluate the role of peripheral blood mtDNA copy number as a biomarker of MS and its progression in relapsing remitting MS (RRMS) patients (which constitute 87% of MS patients) and healthy subjects. In this regards, the present study assessed circulating mtDNA copy number in 25 RRMS patients and 25 age and sex matched healthy control to investigate its role as a potential biomarker of MS.
For this purpose, samples were collected from RRMS patients twice, once during relapse and the other during remission phase, patients were recruited from MS clinic at Neurology Department of Ain Shams University Hospitals. All individuals enrolled in this study were subjected to full history taking, thorough clinical examination especially neurological examination, expanded disability status scale (EDSS) (for patients only), mtDNA copy number quantification by real time polymerase chain reaction (qPCR). Patients with other autoimmune diseases, other neurodegenerative diseases as Parkinsonism and Alzheimer’s disease, malignancy, and type 2 Diabetes Mellitus were excluded from this study.
Results of our study revealed a highly statistically significant decrease in the mtDNA CN in peripheral blood of RRMS patients during remission phase when compared to the control group (p<0.01). In comparison with healthy controls, mtDNA CN values were higher in RRMS patients in relapse, but did not reach statistical significance (p>0.05). Paired comparison between mtDNA CN in remission and relapse phases in RRMS patients’ groups showed significant higher values of mtDNA CN in relapse phase versus remission phase (p<0.05).
By stratifying RRMS patients into two groups according to disease duration to less than or more than 6 years: during relapse, RRMS patients whose duration of illness is less than 6 years and patients whose duration of illness is more than 6 years showed mtDNA CN values comparable to the values of healthy subjects (p>0.05, respectively). During remission, RRMS patients with disease duration less than 6 years and patients with disease duration more than 6 years showed significantly lower mtDNA CN when compared to healthy subjects (p<0.01 & p<0.05, respectively). Mitochondrial DNA CN was comparable in patients with disease duration less than 6 years and those with disease duration more than 6 years during relapse and remission phases (p>0.05, respectively).
Correlation study using Spearman’s rank correlation, was performed between mtDNA CN in relapse and EDSS, and showed non-significant correlation (p>0.05). In remission, mtDNA CN showed non significant correlation with EDSS (p>0.05), while, a highly significant positive correlation with mtDNA CN in relapse (p<0.01). Moreover, ROC curve was applied to discriminate between mtDNA CN of RRMS patients in remission and their mtDNA CN in relapse, at a cut off value (1) AUC was 0.643 with (95% CI 0.522– 0.764).
By using (ROC) curve analysis, our results showed that at a cut off value of (0.75), mtDNA CN discriminated between RRMS patients in remission phase and healthy controls with a sensitivity 56%, specificity 84%, negative predictive value (NPV) 65.6% and positive predictive value (PPV) 77.8%. The (AUC) was 0.598 (95% CI: 0.469-0.726).