Evaluation of Age-Dependent Immune Signatures in Patients With Multiple Sclerosis.

Adult Age Factors Aging / blood CD8-Positive T-Lymphocytes / immunology Cohort Studies Female Humans Male Middle Aged Multiple Sclerosis, Chronic Progressive / blood Multiple Sclerosis, Relapsing-Remitting / blood

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
11 2021
Historique:
received: 05 03 2021
accepted: 30 08 2021
entrez: 20 10 2021
pubmed: 21 10 2021
medline: 5 2 2022
Statut: epublish

Résumé

In MS, an age-related decline in disease activity and a decreased efficacy of disease-modifying treatment have been linked to immunosenescence, a state of cellular dysfunction associated with chronic inflammation. To evaluate age-related immunologic alterations in MS, we compared immune signatures in peripheral blood (PB) and CSF by flow cytometry in patients with relapsing-remitting (RR) (PB n = 38; CSF n = 51) and primary progressive (PP) MS (PB n = 40; CSF n = 36) and respective controls (PB n = 40; CSF n = 85). Analysis revealed significant age-related changes in blood immune cell composition, especially in the CD8 T-cell compartment of healthy donors (HDs) and patients with MS. However, HDs displayed a strong age-dependent decline in the expression of the immunoregulatory molecules KLRG1, LAG3, and CTLA-4 on memory CD8 T cells, whereas this age-dependent reduction was completely abrogated in patients with MS. An age-dependent increase in the expression of the costimulatory molecule CD226 on memory CD8 T cells was absent in patients with MS. CD226 expression correlated with disability in younger (≤50 years) patients with MS. CSF analysis revealed a significant age-dependent decline in various immune cell populations in PPMS but not RRMS, suggesting a differential effect of aging on the intrathecal compartment in PPMS. Our data illustrate that aging in MS is associated with a dysbalance between costimulatory and immunoregulatory signals provided by CD8 T cells favoring a proinflammatory phenotype and, more importantly, a pattern of premature immune aging in the CD8 T-cell compartment of young patients with MS with potential implications for disease severity.

Sections du résumé

BACKGROUND AND OBJECTIVES
In MS, an age-related decline in disease activity and a decreased efficacy of disease-modifying treatment have been linked to immunosenescence, a state of cellular dysfunction associated with chronic inflammation.
METHODS
To evaluate age-related immunologic alterations in MS, we compared immune signatures in peripheral blood (PB) and CSF by flow cytometry in patients with relapsing-remitting (RR) (PB n = 38; CSF n = 51) and primary progressive (PP) MS (PB n = 40; CSF n = 36) and respective controls (PB n = 40; CSF n = 85).
RESULTS
Analysis revealed significant age-related changes in blood immune cell composition, especially in the CD8 T-cell compartment of healthy donors (HDs) and patients with MS. However, HDs displayed a strong age-dependent decline in the expression of the immunoregulatory molecules KLRG1, LAG3, and CTLA-4 on memory CD8 T cells, whereas this age-dependent reduction was completely abrogated in patients with MS. An age-dependent increase in the expression of the costimulatory molecule CD226 on memory CD8 T cells was absent in patients with MS. CD226 expression correlated with disability in younger (≤50 years) patients with MS. CSF analysis revealed a significant age-dependent decline in various immune cell populations in PPMS but not RRMS, suggesting a differential effect of aging on the intrathecal compartment in PPMS.
DISCUSSION
Our data illustrate that aging in MS is associated with a dysbalance between costimulatory and immunoregulatory signals provided by CD8 T cells favoring a proinflammatory phenotype and, more importantly, a pattern of premature immune aging in the CD8 T-cell compartment of young patients with MS with potential implications for disease severity.

Identifiants

DOI: 10.1212/NXI.0000000000001094 PMID: 34667129 PMC: PMC8529419
pubmed: 34667129
pii: 8/6/e1094
doi: 10.1212/NXI.0000000000001094
pmc: PMC8529419
pii:
doi:

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Melanie Eschborn (M)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.
ORCID: 0000-0003-4287-2678

Marc Pawlitzki (M)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Timo Wirth (T)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Christopher Nelke (C)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Steffen Pfeuffer (S)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.
ORCID: 0000-0001-5171-4845

Andreas Schulte-Mecklenbeck (A)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.
ORCID: 0000-0003-3855-4706

Lisa Lohmann (L)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Leoni Rolfes (L)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Katrin Pape (K)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Maria Eveslage (M)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Stefan Bittner (S)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Catharina C Gross (CC)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Tobias Ruck (T)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Heinz Wiendl (H)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Sven G Meuth (SG)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia.

Luisa Klotz (L)

From the Department of Neurology with Institute of Translational Neurology (M. Eschborn, M.P., T.W., S.P., A.S.-M., L.L., C.C.G., H.W., L.K.), University Hospital Münster, Münster, Germany; Department of Neurology with Institute of Translational Neurology (C.N., L.R., T.R., S.G.M.), University Hospital Münster, Münster, Germany; present address: Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany; Department of Neurology (K.P., S.B.), Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Institute of Biostatistics and Clinical Research (M. Eveslage), University of Münster, Münster, Germany; and Brain and Mind Centre (H.W.), Medical Faculty, University of Sydney, Sydney, Camperdown, NSW, Australia. luisa.klotz@ukmuenster.de.
ORCID: 0000-0001-5439-9633

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs âges › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Sclérose en plaques chronique progressive › Evaluation of Age-Dependent Immune Signatures...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Sclérose en plaques récurrente-rémittente › Evaluation of Age-Dependent Immune Signatures...