Increased Myeloid-Derived Suppressor Cells in Newly Diagnosed Multiple Sclerosis: Immunophenotyping and Functional Validation.

Introduction: Myeloid-derived suppressor cells (MDSCs) are key regulators of immune responses during chronic inflammation. Their role in early multiple sclerosis (MS) remains incompletely defined. We aimed to evaluate circulating monocytic (M-MDSC) and polymorphonuclear (PMN-MDSC) levels in newly diagnosed, treatment-naïve MS patients and to assess their functional suppressive capacity. Methods: Eighteen newly diagnosed MS patients and ten age- and sex-matched healthy controls were included. Peripheral blood MDSC subsets were quantified by flow cytometry. Clinical characteristics, MRI findings, and cerebrospinal fluid (CSF) parameters were recorded. Proof-of-concept functional validation was performed using T-cell proliferation assays assessed using CFSE fluorescence dilution by flow cytometry. Results: Both M-MDSC and PMN-MDSC percentages were significantly higher in MS patients compared with controls (p<0.001 for both). Myeloid-derived suppressor cell levels did not differ according to sex and showed no correlation with time from symptom onset, MRI activity, or CSF parameters. Functionally, sorted MDSC subsets suppressed activated T-cell proliferation. Conclusion: Newly diagnosed, untreated MS patients exhibit an expansion of circulating MDSCs with preserved suppressive capacity. These findings suggest that early MS may involve a systemic immunoregulatory response that is not fully captured by conventional clinical or radiological measures.