Сравнительный анализ протеолитических профилей плазмы у пациентов с множественным склерозом с историей COVID-19 и без нее.
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Kot Larysa, Strubchevska Olena, Halenova Tetiana, Strubchevska Kateryna, Raksha Nataliia, Vovk Tetiana, Melnyk Volodymyr, Falalyeyeva Tetyana, Savchuk Olexii
Аннотация
Оригинал публикации
Comparative analysis of plasma proteolytic profiles in multiple sclerosis patients with and without a history of COVID-19.
BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative disorder of the central nervous system characterized by abnormal proteolytic activity-particularly involving serine proteases-that contributes to neuroinflammation and tissue damage. The COVID-19 pandemic has raised concerns about long-term immune and metabolic disturbances that may exacerbate MS progression. This study compared plasma proteolytic profiles in MS patients with and without prior COVID-19, focusing on serine protease composition, molecular organization, and middle-mass molecule (MMM) levels as markers of proteolytic imbalance and systemic metabolic changes.
METHODS: A total of 127 participants aged 35-45 years were recruited from the University Clinic, Bogomolets National Medical University (Kyiv, Ukraine). Ninety-seven had MS and were divided into two groups: MS with COVID-19 (n = 41; confirmed SARS-CoV-2 infection 3-6 months prior) and MS without COVID-19 (n = 56). Thirty healthy volunteers served as controls. Proteolytic activity was assessed via fibrinogen- and gelatin-substrate zymography. Serine protease fractions were isolated by affinity chromatography and quantified by the Bradford assay. Protein composition was analyzed by SDS-PAGE under nonreducing and reducing conditions.
RESULTS: In MS patients, zymography revealed altered proteolytic profiles with a shift toward high-molecular-weight fibrinogenolytic complexes and redistribution of gelatinolytic activity. These changes were more pronounced in those with prior COVID-19. Total plasma serine protease levels were significantly higher in MS patients, particularly in the post-COVID-19 group, which also showed notable alterations in molecular composition and activity patterns. Moreover, MMM peptide fractions related to nonaromatic and aromatic compounds were markedly reduced, especially in post-COVID-19 MS patients, indicating systemic metabolic disturbances.
CONCLUSIONS: MS is associated with persistent quantitative and qualitative changes in plasma proteolytic activity, further amplified by prior SARS-CoV-2 infection. The combination of elevated serine protease levels, high-molecular-weight complex formation, and depletion of specific MMM fractions suggests a sustained imbalance in protease homeostasis. These alterations may contribute to chronic inflammation, endothelial dysfunction, and extracellular matrix remodeling. Plasma protease profiling could serve as a diagnostic and therapeutic tool in MS, particularly for monitoring post-COVID-19 complications.