Identification of circulating MOG-specific B cells in patients with MOG antibodies
Stephan Winklmeier1, Miriam Schlüter1, Melania Spadaro1
1From 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.
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.
