Journal
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
Volume 6, Issue 6, Pages -Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/NXI.0000000000000625
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Funding
- DFG [SFB TR128]
- Munich Cluster for Systems Neurology (EXC 1010 SyNergy)
- Munich Cluster for Systems Neurology (EXC 2145 SyNergy) [390857198]
- Clinical Competence Network for Multiple Sclerosis
- European Academy of Neurology
- Scientific and Technological Research Council of Turkey (TUBITAK) 2219 Program
- Alexander von Humboldt Foundation
- Werner Reichenberger Stiftung
- Verein zur Therapieforschung fur Multiple Sklerose-Kranke
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Objective 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. Methods 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. Results 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. Conclusions 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.
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