Blood immunophenotyping of multiple sclerosis patients at diagnosis identifies a classical monocyte subset associated to disease evolution

Introduction: Myeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes. Methods: Combination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing. Results: Myeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis. Notably, this patients’ subgroup exhibited a more aggressive disease phenotype two years post-diagnosis. This monocytic population, detected in both the CSF and blood, was characterized by CD206, CD209, CCR5 and CCR2 expression, and was found to be more frequent in MS patients carrying the HLA-DRB1*15:01 allele. Furthermore, pathways analysis predicted that these cells had antigen presentation capabilities coupled with pro-inflammatory phenotype. Discussion: Altogether, these results point toward the amplification of a specific and pathogenic myeloid cell subset in MS patients with genetic susceptibilities.