Journal article
Differential binding of autoantibodies to MOG isoforms in inflammatory demyelinating diseases
- Abstract:
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Objective
To analyze serum immunoglobulin G (IgG) antibodies to major isoforms of myelin oligodendrocyte glycoprotein (MOG-alpha 1-3 and beta 1-3) in patients with inflammatory demyelinating diseases.
Methods
Retrospective case-control study using 378 serum samples from patients with multiple sclerosis (MS), patients with non-MS demyelinating disease, and healthy controls with MOG alpha-1-IgG positive (n = 202) or negative serostatus (n = 176). Samples were analyzed for their reactivity to human, mouse, and rat MOG isoforms with and without mutations in the extracellular MOG Ig domain (MOG-ecIgD), soluble MOG-ecIgD, and myelin from multiple species using live cell-based, tissue immunofluorescence assays and ELISA.
Results
The strongest IgG reactivities were directed against the longest MOG isoforms alpha-1 (the currently used standard test for MOG-IgG) and beta-1, whereas the other isoforms were less frequently recognized. Using principal component analysis, we identified 3 different binding patterns associated with non-MS disease: (1) isolated reactivity to MOG-alpha-1/beta-1 (n = 73), (2) binding to MOG-alpha-1/beta-1 and at least one other alpha, but no beta isoform (n = 64), and (3) reactivity to all 6 MOG isoforms (n = 65). The remaining samples were negative (n = 176) for MOG-IgG. These MOG isoform binding patterns were associated with a non-MS demyelinating disease, but there were no differences in clinical phenotypes or disease course. The 3 MOG isoform patterns had distinct immunologic characteristics such as differential binding to soluble MOG-ecIgD, sensitivity to MOG mutations, and binding to human MOG in ELISA.
Conclusions
The novel finding of differential MOG isoform binding patterns could inform future studies on the refinement of MOG-IgG assays and the pathophysiologic role of MOG-IgG.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.0MB, Terms of use)
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- Publisher copy:
- 10.1212/nxi.0000000000001027
Authors
+ Wellcome Trust
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- Funder identifier:
- https://ror.org/029chgv08
- Grant:
- 104079/Z/14/Z
+ FWF Austrian Science Fund
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- Funder identifier:
- https://ror.org/013tf3c58
- Grant:
- P 32699
- Publisher:
- Lippincott, Williams & Wilkins
- Journal:
- Neurology, Neuroimmunology and Neuroinflammation More from this journal
- Volume:
- 8
- Issue:
- 5
- Article number:
- e1027
- Place of publication:
- United States
- Publication date:
- 2021-06-15
- Acceptance date:
- 2021-04-15
- DOI:
- EISSN:
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2332-7812
- Pmid:
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34131067
- Language:
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English
- Pubs id:
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1184259
- Local pid:
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pubs:1184259
- Deposit date:
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2025-02-07
- ARK identifier:
Terms of use
- Copyright holder:
- Schanda et al
- Copyright date:
- 2021
- Rights statement:
- ©2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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