Identification of circulating MOG-specific B cells in patients with MOG antibodies.


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 2019
Historique:
received: 07 06 2019
accepted: 20 08 2019
entrez: 16 10 2019
pubmed: 16 10 2019
medline: 2 10 2020
Statut: epublish

Résumé

To identify circulating myelin oligodendrocyte glycoprotein (MOG)-specific B cells in the blood of patients with MOG antibodies (Abs) and to determine whether circulating MOG-specific B cells are linked to levels and epitope specificity of serum anti-MOG-Abs. We compared peripheral blood from 21 patients with MOG-Abs and 26 controls for the presence of MOG-specific B cells. We differentiated blood-derived B cells in vitro in separate culture wells to Ab-producing cells via engagement of Toll-like receptors 7 and 8. We quantified the anti-MOG reactivity with a live cell-based assay by flow cytometry. We determined the recognition of MOG epitopes with a panel of mutated variants of MOG. MOG-Ab-positive patients had a higher frequency of MOG-specific B cells in blood than controls, but MOG-specific B cells were only detected in about 60% of these patients. MOG-specific B cells in blood showed no correlation with anti-MOG Ab levels in serum, neither in the whole group nor in the untreated patients. Epitope analysis of MOG-Abs secreted from MOG-specific B cells cultured in different wells revealed an intraindividual heterogeneity of the anti-MOG autoimmunity. This study shows that patients with MOG-Abs greatly differ in the abundance of circulating MOG-specific B cells, which are not linked to levels of MOG-Abs in serum suggesting different sources of MOG-Abs. Identification of MOG-specific B cells in blood could be of future relevance for selecting patients with MOG-Abs for B cell-directed therapy.

Identifiants

pubmed: 31611268
pii: 6/6/625
doi: 10.1212/NXI.0000000000000625
pmc: PMC6857907
doi:

Substances chimiques

Autoantibodies 0
MOG protein, human 0
Myelin-Oligodendrocyte Glycoprotein 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

625

Commentaires et corrections

Type : ErratumIn
Type : ErratumIn

Informations de copyright

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Stephan Winklmeier (S)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Miriam Schlüter (M)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Melania Spadaro (M)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Franziska S Thaler (FS)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Atay Vural (A)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Ramona Gerhards (R)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Caterina Macrini (C)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Simone Mader (S)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Aslı Kurne (A)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Berin Inan (B)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Rana Karabudak (R)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Feyza Gül Özbay (FG)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Gunes Esendagli (G)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Reinhard Hohlfeld (R)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Tania Kümpfel (T)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany.

Edgar Meinl (E)

From the Institute of Clinical Neuroimmunology (S.W., M. Schlüter, M. Spadaro, F.S.T., A.V., R.G., C.M., S.M., R.H., T.K., E.M.), Biomedical Center and University Hospitals, Ludwig Maximilian University Munich, Germany; Research Center for Translational Medicine (A.V.), Koç University School of Medicine, Istanbul, Turkey; Department of Neurology, (A.K., B.I., R.K.), Hacettepe University Faculty of Medicine, Ankara, Turkey; Department of Basic Oncology (F.G.Ö., G.E.), Hacettepe University Cancer Institute, Ankara Turkey; and Munich Cluster for Systems Neurology (SyNergy) (R.H.), Germany. edgar.Meinl@med.uni-muenchen.de.

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