Cell-specific proteome profiling reveals altered peripheral immune cell communication in early multiple sclerosis - Nature
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AbstractBackgroundMultiple sclerosis (MS) is characterized by immune dysregulation, yet the molecular alterations present at disease onset remain incompletely understood. We sought to characterize immune cell-specific proteomic changes before treatment initiation in early MS and assess their impact on immune cell communication. MethodsWe performed high-resolution proteomic profiling of four major peripheral immune cell populations, CD4+ and CD8+ T cells, CD19+ B cells, and CD14+ monocytes, from newly diagnosed, treatment-naïve individuals with MS and matched healthy controls. Differential protein expression, pathway enrichment, genetic overlap, and ligand–receptor analyses were performed. ResultsAll four immune cell populations exhibit distinct proteomic alterations that discriminate individuals with MS from healthy controls. Differentially expressed proteins are enriched in pathways related to coagulation, antigen processing, vesicle trafficking, oxidative phosphorylation, and cellular stress responses. Disease-associated proteins overlap with established MS susceptibility genes, with the strongest enrichments observed in CD14⁺ monocytes and CD19⁺ B cells.
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