CyTOF; IgD+CD27+ unswitched memory b cells; autoimmunity; immunology; immunophenotyping; rheumatoid arthritis; Tumor Necrosis Factor Receptor Superfamily, Member 7; Immunoglobulin D; Humans; Male; Middle Aged; Female; Adult; Flow Cytometry; Aged; Arthritis, Rheumatoid/immunology; Arthritis, Rheumatoid/metabolism; Immunophenotyping/methods; Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism; Immunoglobulin D/metabolism; B-Lymphocytes/metabolism; B-Lymphocytes/immunology; Memory B Cells/metabolism; Memory B Cells/immunology; Arthritis, Rheumatoid; B-Lymphocytes; Memory B Cells; Cell Biology
Abstract :
[en] Objectives: Over the past decades, the prevalence of noncommunicable diseases has surged significantly, including the systemic autoimmune disorder rheumatoid arthritis (RA). Despite extensive research and advancement of RA therapy, effective prevention strategies or cures remain elusive, and the mechanisms underlying RA pathogenesis unclear. It is crucial to gain deeper insights into RA pathophysiology. The objective of this study is to provide a comprehensive immunophenotyping of patients with RA. Methods: We generated and analyzed deep immunophenotyping data from 52 patients with RA and 47 healthy controls (HCs). Whole blood samples were stained with extracellular markers, and intracellular antibodies and analyzed for 32 different cell markers using mass cytometry by time of flight. The acquired data was analyzed by both manual and automatic unsupervised tools and subsequently complemented with anthropometric data and clinical-laboratory parameters. Results: We observed a significant disparity in immune cell profiles between patients with RA and HC, notably a reduced frequency of CD27+IgD+ unswitched memory B (mB) cells in patients with RA (p-value < 0.01), with the disease RA being the primary and only significant factor explaining up to 17.9% of the variance of these cells. Conclusion: Our results reveal, for the first time, that a reduced frequency of unswitched mB cells in patients with RA is the only significant abnormality distinguishing patients with RA from HC in a complex immunophenotyping panel of 72 different cell populations. This provides important information to further individualize various interventions and possibly help to design novel therapeutic interventions.
Disciplines :
Life sciences: Multidisciplinary, general & others
RUMP, Kirsten ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Clinical and Translational Informatics
PETROV, Viacheslav ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology
Michalsen, Andreas ; Epidemiology and Health Economics, Institute of Social Medicine, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany ; Department of Internal Medicine and Nature-Based Therapies, Immanuel Hospital Berlin, Berlin, Germany
Hanslian, Etienne ; Epidemiology and Health Economics, Institute of Social Medicine, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany ; Department of Internal Medicine and Nature-Based Therapies, Immanuel Hospital Berlin, Berlin, Germany
Koppold, Daniela A ; Epidemiology and Health Economics, Institute of Social Medicine, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany ; Department of Internal Medicine and Nature-Based Therapies, Immanuel Hospital Berlin, Berlin, Germany
Khokhar, Anika Rajput ; Department of Dermatology, Venereology and Allergology, Charité Universitätsmedizin Berlin, Berlin, Germany
Steckhan, Nico ; Epidemiology and Health Economics, Institute of Social Medicine, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany ; Digital Health-Connected Healthcare, Hasso Plattner Institute, University of Potsdam, Potsdam, Germany
Jeitler, Michael ; Epidemiology and Health Economics, Institute of Social Medicine, Charité - Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany ; Department of Internal Medicine and Nature-Based Therapies, Immanuel Hospital Berlin, Berlin, Germany ; Institute for General Practice and Interprofessional Care, University Hospital Tuebingen, Tuebingen, Germany ; Robert Bosch Center for Integrative Medicine and Health, Bosch Health Campus, Stuttgart, Germany
Mollenhauer, Brit ; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany ; Paracelsus-Elena-Klinik Kassel, Kassel, Germany
Schade, Sebastian ; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany ; Paracelsus-Elena-Klinik Kassel, Kassel, Germany
Vaillant, Michel ; Department of Medical Informatics, Luxembourg Institute of Health, Strassen, Luxembourg
COSMA, Antonio ; University of Luxembourg ; Department of Translational Medicine Operations Hub (TMOH), Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
WILMES, Paul ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology
SCHNEIDER, Jochen ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Medical Translational Research ; Department of Internal Medicine, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany
H2020 - 863664 - ExpoBiome - Deciphering the impact of exposures from the gut microbiome-derived molecular complex in human health and disease
FnR Project :
FNR11823097 - MICROH-DTU - Microbiomes In One Health, 2017 (01/09/2018-28/02/2025) - Paul Wilmes
Funders :
European Research Council European Union
Funding text :
This project has received funding from the European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation programme (grant agreement No. 863664), and was further supported by the Luxembourg National Research Fund (FNR) PRIDE/11823097 (MICROH DTU). We thank Audrey Frachet-Bour, Janine Habier, Jordan Caussin, L\u00E9a Grandmougin, Dr. Catharina Delebinski, Melanie Dell\u2019Oro, Grit Langhans, Ursula Reu\u00DF, Maik Schr\u00F6der, and Nadine Sylvester for their support during the study.This project has received funding from the European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation programme (grant agreement No. 863664), and was further supported by the Luxembourg National Research Fund (FNR) PRIDE/11823097 (MICROH DTU).
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