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Differential Binding of Autoantibodies to MOG Isoforms in Inflammatory Demyelinating Diseases.
- Source :
-
Neurology(R) neuroimmunology & neuroinflammation [Neurol Neuroimmunol Neuroinflamm] 2021 Jun 15; Vol. 8 (5). Date of Electronic Publication: 2021 Jun 15 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Subjects :
- Case-Control Studies
Demyelinating Diseases immunology
Encephalitis immunology
Female
Humans
Male
Multiple Sclerosis immunology
Multiple Sclerosis metabolism
Myelin-Oligodendrocyte Glycoprotein immunology
Protein Binding
Protein Isoforms metabolism
Retrospective Studies
Autoantibodies metabolism
Demyelinating Diseases metabolism
Encephalitis metabolism
Myelin-Oligodendrocyte Glycoprotein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2332-7812
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Neurology(R) neuroimmunology & neuroinflammation
- Publication Type :
- Academic Journal
- Accession number :
- 34131067
- Full Text :
- https://doi.org/10.1212/NXI.0000000000001027