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

Neurol Neuroimmunol Neuroinflamm. 2019 Oct 14;6(6):625. doi: 10.1212/NXI.0000000000000625. Print 2019 Nov.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / blood*
  • Autoimmune Diseases of the Nervous System / blood*
  • Autoimmune Diseases of the Nervous System / immunology*
  • B-Lymphocytes / immunology*
  • Cells, Cultured
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Young Adult

Substances

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