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

Front Immunol

January 2025

Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche U1236, Université Rennes, Etablissement Français du Sang Bretagne, LabEx IGO, Rennes, France.

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.

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Pediatric-Onset Multiple Sclerosis (POMS) is characterized by both white and grey matter inflammation, as well as by a higher risk of long-term physical and cognitive disability. The peculiar immunopathogenic mechanisms of POMS suggests that the use of induction therapies, including alemtuzumab (ALTZ), might be a promising approach, at least for postpuberal (> 11 yo) POMS. Although no data on the use of induction therapies in POMS are available from clinical trials currently, case series or case reports on the effect of alemtuzumab (ALTZ) have been recently published.

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Glycoside hydrolases (GHs) are enzymes involved in the degradation of oligosaccharides and polysaccharides. The sequence space of GHs is rapidly expanding due to the increasing number of available sequences. This expansion paves the way for the discovery of novel enzymes with peculiar structural and functional properties.

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The intramolecular migration of three hydrogen atoms from one moiety of a gaseous radical cation to the other prior to fragmentation is an extremely rare type of redox reaction. Within the scope of this investigation, this scenario requires an ionized but electron-rich arene acceptor bearing a para-(3-hydroxyalkyl) residue. The precise mechanism of such unidirectional 3H transfer processes, including the order of the individual H transfer steps, has remained unclear in spite of previous isotope labelling and recent infrared ion spectroscopy (IRIS) studies.

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The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.

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