This paper explores Multiple Sclerosis (MS), an autoimmune disease affecting the central nervous system, and focuses on identifying biomarkers to predict disease activity. The researchers used high-dimensional flow cytometry to analyze peripheral blood mononuclear cells (PBMCs) from individuals with MS and healthy controls. Their findings highlight HLA-DRhiCD141+ classical monocytes (CMs) as a significant predictor of both impending relapses and disability worsening in patients with active relapsing-remitting MS. This novel biomarker offers a more precise prognostic tool for MS progression, potentially aiding in treatment decisions by complementing existing clinical assessments. The study also suggests that these monocytes could be detected using a simpler, more translational manual gating method, enhancing their practical application in clinical settings.