Microglial activation and toxic astrogliosis are associated with multiple sclerosis (MS) disease process and may partake in central nervous system (CNS) tissue destruction, according to a recent study. In a blinded manner, researchers measured >1,000 proteins in the cerebrospinal fluid (CSF) of 431 patients with neuroimmunological diseases and healthy volunteers using modified DNA-aptamers. They 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). They found:

• 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 pro-inflammatory stimuli and overlap with the phenotype of recently described neuro-toxic (A1) astrocytes.