Platelet miRNA-Based Signature as a Potential Non-Invasive Tool for Discriminating Secondary Progressive Multiple Sclerosis (dataset)

Abstract

Background: Multiple sclerosis (MS) lacks minimally invasive biomarkers that reflect early pathogenic mechanisms. Because blood platelets contribute to throm-bo-inflammatory signaling and are major vascular carriers of regulatory miRNAs, we investigated whether platelet miRNA alterations are associated with platelet hyperre-activity in MS and whether these changes originate during thrombopoiesis by examining megakaryocytes. Methods: Platelets and megakaryocytes from MS patients and healthy controls were analyzed by transmission electron microscopy, flow cytometry, ELISA, microarray-based miRNA profiling, and Real-Time PCR validation. Logistic regression and bioinformatic analyses were used to evaluate biomarker potential and biological relevance. Results: MS platelets exhibited a hyperreactive phenotype, characterized by enhanced degranulation, microparticle release, P-selectin expression, and collagen-induced aggregation. GPVI levels were significantly elevated in platelets but remained un-changed in megakaryocytes. miRNA profiling revealed widespread downregulation in platelets, whereas megakaryocytes showed selective upregulation of miR-223-3p. A two-miRNA model (let-7a-5p and miR-146a-5p) demonstrated strong discriminatory performance (AUC = 0.89; 89% sensitivity; 85% specificity). Dysregulated miRNAs were associated with pathways involved in neuroinflammation and neurodegeneration. Conclusions: MS is associated with a distinct platelet miRNA signature linked to acquired platelet hyperreactivity and vesiculation. Platelet-derived let-7a-5p and miR-146a-5p represent promising non-invasive biomarkers supporting a mechanistic link between platelet dysfunction, vascular injury, and neuroinflammation in MS.