مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Molecular Signatures of MS: Diagnostic and Prognostic Epigenetic Biomarkers
Molecular Signatures of MS: Diagnostic and Prognostic Epigenetic Biomarkers
Amir Hossein Kiani Darabi,1Saba Hadi,2Seyed Hossein Khoshraftar,3Maryam Rezazadeh,4,*
1. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 4. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Introduction: Multiple sclerosis (MS) is a long-term autoimmune condition that targets the central nervous system (CNS), resulting in gradual damage to the myelin sheath and causing various neurological complications. Like many autoimmune diseases, MS is more commonly seen in women than in men, with an estimated ratio of three women for every one man. It is most frequently identified in early adulthood, especially among individuals aged 20 to 40.A major obstacle in the clinical handling of MS is the lack of effective tools for early diagnosis and precise prediction of disease progression in its early phases. Presently, prognostic assessments are largely dependent on clinical observations and MRI-based brain imaging, which emphasize the detection of structural abnormalities like lesions and brain atrophy. Nevertheless, these approaches typically reveal neuronal damage only after it has taken place, potentially when the injury to the central nervous system is already permanent.In contrast, molecular biomarkers, including epigenetic indicators, have introduced novel strategies for the early diagnosis and more accurate prognosis of MS. For instance, neurofilament protein subunits, which are key components of the axonal cytoskeleton, as well as circulating cell-free DNA (cfDNA), can detect neurodegenerative processes in the early stages of the disease and may provide opportunities for timely therapeutic intervention.Recent research has shown a notable rise in cfDNA levels in the bloodstream of individuals with MS, which correlates with the intensity of the disease and the number of relapses. As a result, cfDNA holds potential as a sensitive biomarker for both diagnosing MS and forecasting its progression.Moreover, microRNAs (miRNAs)—small, non-coding RNA molecules typically 19–25 nucleotides long—have attracted considerable interest due to their remarkable stability, resistance to degradation by endogenous RNases, presence in bodily fluids, and responsiveness to physiological changes. These molecules are key regulators of immune and inflammatory mechanisms involved in MS. For example, miR-155 and miR-326 are known to play important roles in modulating immune cell activity during relapse episodes. Additionally, decreased expression of miRNAs such as miR-17 and miR-20a in MS patients highlights their potential as biomarkers for tracking disease progression and assessing therapeutic outcomes. On the other hand, circular RNAs (circRNAs) are a class of non-coding RNAs with diverse biological functions. These molecules can directly or indirectly influence tight and adherens junctions by regulating upstream signaling pathways and transcription factors. Therefore, circRNAs have emerged as promising therapeutic targets for the restoration of the blood-brain barrier (BBB). In addition, due to their high stability and detectability in biological fluids such as plasma and saliva, circRNAs are currently being explored as non-invasive biomarkers in MS. Among them, hsa-circ-0074158 has been identified as one of the most significant circRNAs studied and is considered a potential therapeutic target for the diagnosis and monitoring of MS.
Methods: A significant number of influential articles published between 2017 and 2025 were systematically reviewed and analyzed through searches in reputable databases such as PubMed, Google Scholar, and others. The results of these studies have been compiled and presented in this article.
Results: The results indicate that cfDNA levels are significantly elevated in patients with MS, and this increase is directly associated with disease severity and relapse frequency. Additionally, miRNAs such as miR-155 and miR-326 exhibit altered expression during active phases of the disease, suggesting their involvement in immune responses related to relapses. Furthermore, circular RNAs—particularly hsa-circ-0074158—may serve as reliable biomarkers for the early diagnosis of MS and for monitoring therapeutic responses.
Conclusion: Given the recent advances in epigenetics and the identification of molecular markers, tools such as cfDNA, miRNAs, and circRNAs are expected to play a significant role in the diagnosis, prognosis, and clinical management of MS in the near future. These biomarkers not only offer the potential for early disease detection but may also contribute to improved prognostic accuracy and the development of personalized treatment strategies. However, extensive clinical studies are still needed to translate these findings into practical applications in clinical settings.