Charakterystyka kompleksów płytkowo-leukocytarnych i analiza ekspresji miRNA jako wskaźników stanu zapalnego i neurodegeneracji w rzutowo-remisyjnej i wtórnie postępującej postaci stwardnienia rozsianego

Abstract

Multiple sclerosis (MS) is a chronic neurodegenerative disease with an autoimmune background primarily affecting the central nervous system (CNS). The most common form of the condition is inflammatory relapsing-remitting MS (RRMS), whereas secondary progressive MS (SPMS), which typically develops after RRMS, is characterized by progressive neurodegeneration. However, recent reports indicate coexistence of inflammatory and neurodegenerative features in both phenotypes, complicating early differentiation, therapeutic decisions, and prognosis. The primary objective of the research was to identify markers enabling differentiation of disease phenotypes in patients with RRMS in remission and SPMS. In the first stage, platelet-leukocyte hetero-aggregates (PLAs) were characterized as elements linking vascular injury with inflammation. Increased leukocyte chemotaxis toward platelets and PLAs formation, predominantly involving B-cells, were demonstrated in MS. Next, screening of miRNA expression from extracellular vesicles (EVs) was conducted, followed by measurement of inflammatory cytokines and markers of neuronal/glial damage in plasma. A model combining miRNA expression with basic fibroblast growth factor achieved an AUC of 0.97, confirming its high ability to discriminate RRMS and SPMS. In the third stage, EVs presenting L1CAM, a protein used to enrich the neuronal fraction of EVs, were characterized in serum and cerebrospinal fluid to assess their usefulness as biomarkers for monitoring response to rituximab treatment, an anti-CD20 monoclonal antibody, in RRMS patients. In summary, the research expands understanding of MS pathophysiology, linking immune response with vascular injury, and identifies opportunities for non-invasive biomarkers to differentiate RRMS and SPMS as well as to monitor CNS immunopathology and treatment response.