Department of Clinical Pathology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Department of Neurology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Egypt J Immunol. 2023 Oct;30(4):121-133.
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). In its early stages, it results in inflammation, demyelination, and axonal loss. Egypt has the highest rates in the Middle East region. The pathogenicity of MS involves mitochondrial function. Damage to mitochondrial DNA (mtDNA) can produce variation in the copy number (CN) and decline in mitochondrial function. Our goal was to determine the potential of mtDNA-CN as a biomarker of MS and the progression of the disease. The study included 25 patients with relapsing remitting MS (RRMS) and 25 age and sex matched apparently healthy control. Two peripheral blood samples were collected from each patient, one during the remission phase and the other during the phase of relapse. A quantitative real-time polymerase chain reaction (qPCR) was performed to assess CN of mitochondrial DNA. There was a statistically significant decline in the number of mtDNA copies during the remission phase as compared to controls (p < 0.01), yet no difference was seen between mtDNA-CN in relapsing subjects versus controls. Moreover, the copy number of mtDNA during the relapse phase was significantly higher than the remission phase suggesting the ability of mtDNA to differentiate between remission and relapse phases (p < 0.05). Our study observed that mtDNA-CN at a cut off (0.75), can differentiate between RRMS patients in the remission phase and controls with a sensitivity of 56%, specificity 84%, positive predictive value (PPV) 65.6% and negative predictive value (NPV) 77.8%, and at a cut off (1), mtDNA-CN can differentiate between remission and relapse MS patients with a sensitivity 72%, specificity 56%, PPV 62.1% and NPV 66.7%. In conclusion, mtDNA-CN can be proposed as a biomarker of MS.
多发性硬化症(MS)是一种影响中枢神经系统(CNS)的慢性自身免疫性疾病。在早期,它会导致炎症、脱髓鞘和轴突丢失。埃及是中东地区发病率最高的国家。MS 的发病机制涉及线粒体功能。线粒体 DNA(mtDNA)的损伤会导致拷贝数(CN)的变化和线粒体功能的下降。我们的目标是确定 mtDNA-CN 作为 MS 及其疾病进展的生物标志物的潜力。该研究包括 25 名复发缓解型多发性硬化症(RRMS)患者和 25 名年龄和性别匹配的健康对照者。从每位患者采集两份外周血样本,一份在缓解期,另一份在复发期。通过定量实时聚合酶链反应(qPCR)评估线粒体 DNA 的 CN。与对照组相比,缓解期 mtDNA 拷贝数有统计学意义的下降(p < 0.01),但复发组与对照组之间的 mtDNA-CN 无差异。此外,在复发期,mtDNA 的拷贝数明显高于缓解期,这表明 mtDNA 能够区分缓解期和复发期(p < 0.05)。我们的研究观察到,在截止值(0.75)处的 mtDNA-CN 可以区分缓解期的 RRMS 患者和对照组,其灵敏度为 56%,特异性为 84%,阳性预测值(PPV)为 65.6%,阴性预测值(NPV)为 77.8%,在截止值(1)处,mtDNA-CN 可以区分缓解期和复发期 MS 患者,其灵敏度为 72%,特异性为 56%,PPV 为 62.1%,NPV 为 66.7%。总之,mtDNA-CN 可以作为 MS 的生物标志物。