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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Platelet miRNA-Based Signature as a Potential Non-Invasive Tool for Discriminating Patients with Secondary Progressive Multiple Sclerosis from Healthy Individuals

  • Angela Dziedzic1
  • Michał Seweryn Karbownik2
  • Michał Arabski3
  • Elżbieta Miller4
  • Sylwia Michlewska5
  • Joanna Saluk1
5 affiliations
  1. 1Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
  2. 2Department of Pharmacology and Toxicology, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland
  3. 3Division of Medical Biology, Institute of Biology, Jan Kochanowski University, Uniwersytecka 7, 25-406 Kielce, Poland
  4. 4Department of Neurological Rehabilitation, Medical University of Lodz, Milionowa 14, 93-113 Lodz, Poland
  5. 5Laboratory of Microscopic Imaging and Specialized Biological Techniques, Faculty of Biology and Environmental Protection, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland
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Abstract

Multiple sclerosis (MS) lacks minimally invasive biomarkers that reliably reflect disease-associated pathophysiological alterations, particularly during the progressive stage of the disease. Because blood platelets contribute to thrombo-inflammatory signalling and are the major vascular carriers of regulatory miRNA, we investigated whether platelet miRNA alterations are associated with platelet hyperreactivity in MS and whether these changes originate during thrombopoiesis by examining megakaryocytes. We analyzed platelets and megakaryocytes from MS patients and healthy controls by transmission electron microscopy, flow cytometry, ELISA, miRNA profiling based on microarrays, and Real-Time PCR validation. Logistic regression and bioinformatic analyses were used to evaluate the potential and biological relevance. 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 unchanged in megakaryocytes. MiRNA profiling revealed widespread downregulation in platelets, while megakaryocytes showed selective upregulation of miR-223-3p. Following microarray screening, PCR validation of 10 selected miRNAs revealed widespread downregulation in platelets, while only miR-223-3p was significantly upregulated in megakaryocytes from MS patients. A two-miRNA model (let-7a-5p and miR-146a-5p) showed good internal discrimination (AUC = 0.89; sensitivity 89%; specificity 85%), but lower external performance (C-index = 0.66; sensitivity 50%; specificity 73%). 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 potential non-invasive biomarker candidates, although their diagnostic utility requires further validation in larger independent cohorts.

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Cite

BibTeXRIS
BibTeX
@article{dziedzic2026platelet,
  title = {{Platelet miRNA-Based Signature as a Potential Non-Invasive Tool for Discriminating Patients with Secondary Progressive Multiple Sclerosis from Healthy Individuals}},
  author = {Angela Dziedzic and Michał Seweryn Karbownik and Michał Arabski and Elżbieta Miller and Sylwia Michlewska and Joanna Saluk},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219914},
  url = {https://www.mdpi.com/1422-0067/27/21/9914},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Platelet miRNA-Based Signature as a Potential Non-Invasive Tool for Discriminating Patients with Secondary Progressive Multiple Sclerosis from Healthy Individuals
AU  - Angela Dziedzic
AU  - Michał Seweryn Karbownik
AU  - Michał Arabski
AU  - Elżbieta Miller
AU  - Sylwia Michlewska
AU  - Joanna Saluk
PY  - 2026
DA  - 2026/11/05
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219914
UR  - https://www.mdpi.com/1422-0067/27/21/9914
AB  - Multiple sclerosis (MS) lacks minimally invasive biomarkers that reliably reflect disease-associated pathophysiological alterations, particularly during the progressive stage of the disease. Because blood platelets contribute to thrombo-inflammatory signalling and are the major vascular carriers of regulatory miRNA, we investigated whether platelet miRNA alterations are associated with platelet hyperreactivity in MS and whether these changes originate during thrombopoiesis by examining megakaryocytes. We analyzed platelets and megakaryocytes from MS patients and healthy controls by transmission electron microscopy, flow cytometry, ELISA, miRNA profiling based on microarrays, and Real-Time PCR validation. Logistic regression and bioinformatic analyses were used to evaluate the potential and biological relevance. 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 unchanged in megakaryocytes. MiRNA profiling revealed widespread downregulation in platelets, while megakaryocytes showed selective upregulation of miR-223-3p. Following microarray screening, PCR validation of 10 selected miRNAs revealed widespread downregulation in platelets, while only miR-223-3p was significantly upregulated in megakaryocytes from MS patients. A two-miRNA model (let-7a-5p and miR-146a-5p) showed good internal discrimination (AUC = 0.89; sensitivity 89%; specificity 85%), but lower external performance (C-index = 0.66; sensitivity 50%; specificity 73%). 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 potential non-invasive biomarker candidates, although their diagnostic utility requires further validation in larger independent cohorts.
SN  - 1422-0067
ER  -