Blood Immunophenotyping in Multiple Sclerosis: A Classical Monocyte Subset Linked to Disease Evolution
A recent study has shed light on the role of myeloid cells in the development and progression of multiple sclerosis (MS). The study, published in *Frontiers in Immunology* on January 8, 2025, and led by Rodriguez et al., investigated the blood immunophenotypes of MS patients at diagnosis to identify potential biomarkers associated with disease evolution. The research team employed a combination of mass cytometry on blood cells from MS patients and healthy controls, along with single-cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from a subset of MS patients. This multi-faceted approach allowed for a detailed characterization of myeloid cells and their potential roles in MS.
Key Findings
* Enrichment of a unique classical monocyte population: The study revealed an enrichment of a specific classical monocyte population in 22% of MS patients at the time of diagnosis. This subgroup of patients exhibited a more aggressive disease phenotype two years post-diagnosis.
* Monocyte Characterization: The unique monocytic population, found in both the CSF and blood, was characterized by the expression of CD206, CD209, CCR5, and CCR2. Furthermore, these monocytes were more frequent in MS patients carrying the HLA-DRB1*15:01 allele, a known genetic susceptibility factor for MS.
* Antigen Presentation and Pro-inflammatory Phenotype: Pathway analysis indicated that these cells possess antigen presentation capabilities coupled with a pro-inflammatory phenotype.
Methods and Materials
The researchers used blood samples from 60 RRMS (relapsing-remitting multiple sclerosis) patients and 29 healthy controls, all of who were drug-naive. Mass cytometry was performed on peripheral blood mononuclear cells (PBMCs) sampled at diagnosis. Unsupervised analysis was then performed on the myeloid compartment, which allowed the researchers to identify a specific population of classical monocytes expressing CD209 and CD206 that were enriched in some MS patients. Single-cell RNA sequencing (scRNA-seq) was performed on paired CSF and blood cells from MS patients, which, along with pathway enrichment analysis, indicated that these cells are present in both CSF and blood, have a pro-inflammatory profile, and have a higher propensity to process and present antigens compared to other classical monocytes.
Monocyte Heterogeneity
Monocytes, typically defined by CD14 and CD16 expression, are a heterogeneous subset comprising classical monocytes (cMo), intermediate monocytes (intMo), and non-classical monocytes (ncMo). These subsets can migrate to tissue lesions, while microglial cells and border-associated macrophages (BAMs) are associated with tissue-derived myeloid cells in human CSF. Infiltrating monocytes can acquire the dendritic cell marker CD209 after crossing the blood-brain barrier (BBB).
Implications for MS Pathogenesis
These findings suggest that the amplification of a specific and pathogenic myeloid cell subset may play a crucial role in MS development in individuals with genetic predispositions. The identified CD206hi CD209hi Mo cells displayed characteristics of activated and tissue-trafficking classical monocytes. Further analysis revealed that a threshold of 1% CD206hi CD209hi Mo frequency among myeloid cells could differentiate healthy controls from MS patients, and among MS patients, those with CD206hi CD209hi Mo enrichment from those without.
Clinical Significance
MS patients with CD206hi CD209hi Mo cells experienced more inflammatory activity and had higher EDSS (Expanded Disability Status Scale) scores, indicating a poorer prognosis. The study also found a significant association between these cells and the HLA-DRB1*15:01 allele.
Caveats
The authors noted that this study was highly descriptive, and the lack of a validation cohort to confirm their findings is a limitation of this work. They suggest that assessing more patients and controls over a longer period should help in the estimation of CD206hi CD209hi Mo’s contribution to patients’ outcomes, independently of treatments and other confounding factors.
Future Directions
The study opens avenues for future research, including:
* Investigating the mechanisms driving the expansion and activation of this specific monocyte subset.
* Exploring the precise role of HLA-DRB1*15:01 in promoting CD206hi CD209hi Mo cell development.
* Evaluating the therapeutic potential of targeting this monocyte subset to modulate MS disease activity.
Ultimately, a deeper understanding of this pathogenic myeloid cell subset may lead to the development of novel therapeutic strategies for 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., Couloume, L., Ferrant, J., Vince, N., Mandon, M., Jean, R., ... & Michel, L. (2025). Blood immunophenotyping of multiple sclerosis patients at diagnosis identifies a classical monocyte subset associated to disease evolution. Frontiers in Immunology, 15, 1494842.
