Aryl Hydrocarbon Receptor Plasma Agonist Activity Correlates With Disease Activity in Progressive MS.

Basic Helix-Loop-Helix Transcription Factors / agonists Biomarkers / blood Cohort Studies Cross-Sectional Studies Disease Progression HEK293 Cells Humans Longitudinal Studies Magnetic Resonance Imaging / trends Multiple Sclerosis, Chronic Progressive / blood Receptors, Aryl Hydrocarbon / agonists

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:
03 2021
Historique:
received: 12 06 2020
accepted: 29 10 2020
entrez: 28 12 2020
pubmed: 29 12 2020
medline: 29 10 2021
Statut: epublish

Résumé

The relationship between serum aryl hydrocarbon receptor (AHR) agonistic activity levels with disease severity, its modulation over the course of relapsing-remitting MS (RRMS), and its regulation in progressive MS (PMS) are unknown. Here, we report the analysis of AHR agonistic activity levels in cross-sectional and longitudinal serum samples of patients with RRMS and PMS. In a cross-sectional investigation, a total of 36 control patients diagnosed with noninflammatory diseases, 84 patients with RRMS, 35 patients with secondary progressive MS (SPMS), and 41 patients with primary progressive MS (PPMS) were included in this study. AHR activity was measured in a cell-based luciferase assay and correlated with age, sex, the presence of disease-modifying therapies, Expanded Disability Status Scale scores, and disease duration. In a second longitudinal investigation, we analyzed AHR activity in 13 patients diagnosed with RRMS over a period from 4 to 10 years and correlated AHR agonistic activity with white matter atrophy and lesion load volume changes. In RRMS, AHR ligand levels were globally decreased and associated with disease duration and neurologic disability. In SPMS and PPMS, serum AHR agonistic activity was decreased and correlated with disease severity. Finally, in longitudinal serum samples of patients with RRMS, decreased AHR agonistic activity was linked to progressive CNS atrophy and increased lesion load. These findings suggest that serum AHR agonist levels negatively correlate with disability in RRMS and PMS and decrease longitudinally in correlation with MRI markers of disease progression. Thus, serum AHR agonistic activity may serve as novel biomarker for disability progression in MS.

Identifiants

DOI: 10.1212/NXI.0000000000000933 PMID: 33361385 PMC: PMC7768947
pubmed: 33361385
pii: 8/2/e933
doi: 10.1212/NXI.0000000000000933
pmc: PMC7768947
pii:
doi:

Substances chimiques

AHR protein, human 0
Basic Helix-Loop-Helix Transcription Factors 0
Biomarkers 0
Receptors, Aryl Hydrocarbon 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS102807
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Thanos Tsaktanis (T)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Tobias Beyer (T)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Lucy Nirschl (L)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Mathias Linnerbauer (M)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Verena Grummel (V)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Mathias Bussas (M)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Emily Tjon (E)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Mark Mühlau (M)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Thomas Korn (T)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.
ORCID: 0000-0002-3633-0955

Bernhard Hemmer (B)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.
ORCID: 0000-0001-5985-6784

Francisco J Quintana (FJ)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany.

Veit Rothhammer (V)

From the Department of Neurology (T.T., T.B., L.N., M.L., V.G., M.B., M.M., T.K., B.H., V.R.), Klinikum rechts der Isar, Technical University of Munich; Department of Neurology (T.T., V.R.), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg; Munich Cluster for Systems Neurology (SyNergy) (T.K., B.H.), Germany; Ann Romney Center for Neurologic Diseases (E.T., F.J.Q.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Broad Institute of MIT and Harvard (F.J.Q.), Cambridge, MA; and TUM-Neuroimaging Center (M.B., M.M.), Klinikum rechts der Isar, Technische Universität München, Germany. veit.rothhammer@fau.de.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique hélice-boucle-hélice › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études longitudinales › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Sclérose en plaques chronique progressive › Aryl Hydrocarbon Receptor Plasma Agonist...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs à hydrocarbure aromatique › Aryl Hydrocarbon Receptor Plasma Agonist...