https://www.sciencedirect.com/science/a ... 481830525X
HIGHLIGHTS
• Microglial/myeloid cell activation markers are present during all stages of MS.
• Toxic astrocyte specific markers increase with MS duration.
• Aberrant activation of glial cells contributes to CNS tissue destruction and enhance MS severity.
ABSTRACT

Methods: In a blinded manner, we measured over 1000 proteins in the cerebrospinal fluid (CSF) of 431 patients with neuroimmunological diseases and healthy volunteers using modified DNA-aptamers (SOMAscan®). We defined CNS cell type-enriched clusters using variable cluster analysis, combined with in vitro modeling. Differences between diagnostic categories were identified in the training cohort (n = 217) and their correlation to disability measures were assessed; results were validated in an independent validation cohort (n = 214).
Results: Astrocyte cluster 8 (MMP7, SERPINA3, GZMA and CLIC1) and microglial cluster 2 (DSG2 and TNFRSF25) were reproducibly elevated in MS and had a significant and reproducible correlation with MS severity suggesting their pathogenic role. In vitro studies demonstrated that proteins of astrocyte cluster 8 are noticeably released upon stimulation with proinflammatory stimuli and overlap with the phenotype of recently described neuro-toxic (A1) astrocytes.
Conclusion: Microglial activation and toxic astrogliosis are associated with MS disease process and may partake in CNS tissue destruction. This hypothesis should be tested in new clinical trials.