Dataset Information

Mass Cytometry Identifies Expansion of T-bet⁺ B Cells and CD206⁺ Monocytes in Early Multiple Sclerosis.

ABSTRACT: Multiple sclerosis (MS) is an immune-driven demyelinating disease of the central nervous system. Immune cell features are particularly promising as predictive biomarkers due to their central role in the pathogenesis but also as drug targets, even if nowadays, they have no impact in clinical practice. Recently, high-resolution approaches, such as mass cytometry (CyTOF), helped to better understand the diversity and functions of the immune system. In this study, we performed an exploratory analysis of blood immune response profiles in healthy controls and MS patients sampled at their first neurological relapse, using two large CyTOF panels including 62 markers exploring myeloid and lymphoid cells. An increased abundance of both a T-bet-expressing B cell subset and a CD206⁺ classical monocyte subset was detected in the blood of early MS patients. Moreover, T-bet-expressing B cells tended to be enriched in aggressive MS patients. This study provides new insights into understanding the pathophysiology of MS and the identification of immunological biomarkers. Further studies will be required to validate these results and to determine the exact role of the identified clusters in neuroinflammation.

SUBMITTER: Couloume L

PROVIDER: S-EPMC8129576 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Mass Cytometry Identifies Expansion of T-bet<sup>+</sup> B Cells and CD206<sup>+</sup> Monocytes in Early Multiple Sclerosis.

Couloume Laura L Ferrant Juliette J Le Gallou Simon S Mandon Marion M Jean Rachel R Bescher Nadège N Zephir Helene H Edan Gilles G Thouvenot Eric E Ruet Aurelie A Debouverie Marc M Tarte Karin K Amé Patricia P Roussel Mikael M Michel Laure L

Frontiers in immunology 20210504

Multiple sclerosis (MS) is an immune-driven demyelinating disease of the central nervous system. Immune cell features are particularly promising as predictive biomarkers due to their central role in the pathogenesis but also as drug targets, even if nowadays, they have no impact in clinical practice. Recently, high-resolution approaches, such as mass cytometry (CyTOF), helped to better understand the diversity and functions of the immune system. In this study, we performed an exploratory analysi ...[more]

PMID: 34017332

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Project description:Multiple Myeloma (MM) is preceded by the clinically stable condition monoclonal gammopathy of undetermined significance (MGUS). Critical immune events that discriminate MGUS from newly diagnosed MM (ND)MM patients remain unknown, but may involve changes in the regulatory T cell (Treg) compartment that favor myeloma growth. To address this possibility, we used mass cytometry and the unsupervised clustering algorithm Flow self-organizing map (FlowSOM) to interrogate the distribution of multiple subsets within CD25+CD127low/negTreg in matched bone marrow (BM) and peripheral blood (PB) of MGUS and NDMM patients. Both mass cytometry and flow cytometry confirmed a trend toward prevalence of CD39-Treg within the Treg compartment in BM and PB of NDMM patients compared to CD39-Treg in MGUS patients. FlowSOM clustering displayed a phenotypic organization of Treg into 25 metaclusters that confirmed Treg heterogeneity. It identified two subsets which emerged within CD39-Treg of NDMM patients that were negligible or absent in CD39-Treg of MGUS patients. One subset was found in both BM and PB which phenotypically resembled activated Treg based on CD45RO, CD49d, and CD62L expression; another subset resembled BM-resident Treg based on its tissue-resident CD69+CD62L-CD49d- phenotype and restricted location within the BM. Both subsets co-expressed PD-1 and TIGIT, but PD-1 was expressed at higher levels on BM-resident Treg than on activated Treg. Within BM, both subsets had limited Perforin and Granzyme B production, whilst activated Treg in PB acquired high Perforin and Granzyme B production. In conclusion, the use of mass cytometry and FlowSOM clustering discovered two discrete subsets of CD39-Treg which are discordant in MGUS and NDMM patients and may be permissive of myeloma growth which warrants further study. Understanding the regulatory properties of these subsets may also advance MGUS and MM diagnosis, prognosis, and therapeutic implications for MM patients.

Dataset Information

Mass Cytometry Identifies Expansion of T-bet⁺ B Cells and CD206⁺ Monocytes in Early Multiple Sclerosis.

Publications

Mass Cytometry Identifies Expansion of T-bet<sup>+</sup> B Cells and CD206<sup>+</sup> Monocytes in Early Multiple Sclerosis.

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Dataset Information

Mass Cytometry Identifies Expansion of T-bet+ B Cells and CD206+ Monocytes in Early Multiple Sclerosis.

Publications

Mass Cytometry Identifies Expansion of T-bet<sup>+</sup> B Cells and CD206<sup>+</sup> Monocytes in Early Multiple Sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Mass Cytometry Identifies Expansion of T-bet⁺ B Cells and CD206⁺ Monocytes in Early Multiple Sclerosis.