Newly Identified Monocyte Subset Offers Early Clues to Multiple Sclerosis Progression
Multiple sclerosis (MS) — the complex, immune-mediated disease that attacks the central nervous system (CNS) — has long puzzled scientists and clinicians alike. While we know that immune cells infiltrate the brain and spinal cord, triggering inflammation and neurodegeneration, the precise roles of different immune cell types remain a frontier of discovery.
A new study published in Frontiers in Immunology by Laure Michel and colleagues from the French OFSEP consortium sheds light on a previously unrecognized player in this complex immune landscape: a distinct subset of classical monocytes circulating in the blood of MS patients at diagnosis that appears to be linked with disease progression.
Let’s unpack what this means — and why it matters.
The Study in Brief
The researchers used mass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq) to profile immune cells from:
60 newly diagnosed relapsing–remitting MS (RRMS) patients, before any treatment
29 healthy controls
Plus paired blood and cerebrospinal fluid (CSF) samples from five MS patients
Their goal? To look for hidden patterns in the immune system that could predict how the disease evolves.
The Discovery: A Peculiar Monocyte Subset
Among millions of blood cells analyzed, one population stood out. About 22% of MS patients showed an unusually high level of CD206⁺CD209⁺ classical monocytes — cells that were almost absent in healthy individuals.
These monocytes expressed surface markers associated with inflammation and tissue trafficking — notably CCR2, CCR5, CD45RA, and VCAM-1 — suggesting that they are primed to migrate into inflamed tissues, like the brain.
Intriguingly, this monocyte subset was more common in patients carrying the well-known genetic risk allele HLA-DRB1*15:01, hinting at a possible genetic influence on immune cell behavior.
Tracking the Cells into the Brain
Using scRNA-seq on both blood and CSF, the team found CD206⁺CD209⁺ monocyte-like cells not only in circulation but also within the CSF, the fluid bathing the brain and spinal cord.
These cells expressed genes involved in:
Antigen processing and presentation (HLA molecules, CD74)
Pro-inflammatory signaling (IL18, CCR2)
Together, this suggests that once these cells enter the CNS, they may act as antigen-presenting cells, potentially triggering or amplifying autoimmune responses against myelin.
Clinical Relevance: Predicting Disease Evolution
When the researchers followed patients over two years, a clear pattern emerged:
Those with high levels of CD206⁺CD209⁺ monocytes at diagnosis had a poorer prognosis.
They were more likely to experience new inflammatory lesions or relapses.
Their disability scores (EDSS) and age-related MS severity (ARMSS) were higher.
This finding implies that the blood immune profile at diagnosis could serve as an early biomarker of disease aggressiveness — a potential game-changer for personalized MS management.
Why This Matters
Current MS biomarkers, such as neurofilament light chain (NfL) levels or MRI lesion counts, are useful but not perfect predictors of disease activity. The discovery of a blood-based cellular signature tied to disease evolution could complement these tools, especially at the earliest stages of MS when treatment decisions are critical.
Moreover, this study deepens our understanding of how peripheral immune cells communicate with the brain. The CD206⁺CD209⁺ monocytes appear to bridge the peripheral and central immune systems — a conduit through which genetic risk and inflammatory activation may converge.
Broader Implications and Next Steps
The researchers propose that targeting this specific monocyte subset — or the molecules that guide its migration into the CNS — could represent a novel therapeutic avenue. Drugs that block monocyte trafficking (like anti-VLA-4 therapies) already exist in MS treatment; fine-tuning them toward this pathogenic subset could increase efficacy while reducing side effects.
Future studies will need to:
Validate these findings in larger, independent cohorts
Test whether these monocytes persist or change with treatment
Explore their interactions with T cells and the blood–brain barrier
Final Thoughts
This study exemplifies the power of combining cutting-edge single-cell technologies with well-characterized patient cohorts. By zooming in on the immune system at unprecedented resolution, the researchers have identified a potential cellular fingerprint of disease severity in multiple sclerosis.
As Dr. Laure Michel and her team conclude, understanding and potentially disrupting the “monocyte connection” between the blood and the brain might open new paths toward precision immunotherapy in MS.
Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.
References:
Rodriguez S. et al. (2025). Blood immunophenotyping of multiple sclerosis patients at diagnosis identifies a classical monocyte subset associated to disease evolution. Frontiers in Immunology, 15:1494842. DOI: 10.3389/fimmu.2024.1494842
