Anti-MOG autoantibodies pathogenicity in children and macaques demyelinating diseases

Che Serguera*, Lev Stimmer, Claire-Maelle Fovet, Philippe Horellou, Vanessa Contreras, Nicolas Tchitchek, Julie Massonneau, Carole Leroy, Audrey Perrin, Julien Flament, Philippe Hantraye, Joanna Demilly, Romain Marignier, Pascale Chretien, Bertt Hart, Jean Boutonnat, Clovis Adam, Roger Le-Grand, Kumaran Deiva

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
156 Downloads (Pure)

Abstract

Background Autoantibodies against myelin oligodendrocyte glycoprotein (anti-MOG-Abs) occur in a majority of children with acquired demyelinating syndromes (ADS) and physiopathology is still under investigation. As cynomolgus macaques immunized with rhMOG, all develop an experimental autoimmune encephalomyelitis (EAE), we assessed relatedness between anti-MOG-Abs associated diseases in both species. Methods The study includes 27 children followed for ADS and nine macaques with rhMOG-induced EAE. MRI lesions, cytokines in blood, and CSF at onset of ADS or EAE, as well as histopathological features of brain lesions were compared. Results Twelve children with anti-MOG-Abs ADS (ADS MOG+) and nine macaques with EAE, presented increased IL-6 and G-CSF in the CSF, whereas no such signature was found in 15 ADS MOG-. Furthermore, IgG and C1q were associated to myelin and phagocytic cells in brains with EAE (n = 8) and in biopsies of ADS MOG+ (n = 2) but not ADS MOG- children (n = 1). Macaque brains also revealed prephagocytic lesions with IgG and C1q depositions but no leukocyte infiltration. Conclusions Children with ADS MOG+ and macaques with EAE induced with rhMOG, present a similar cytokine signature in the CSF and a comparable aspect of brain lesions indicating analogous pathophysiological processes. In EAE, prephagocytic lesions points at IgG as an initial effector of myelin attack. These results support the pertinence of modeling ADS MOG+ in non-human primates to apprehend the natural development of anti-MOG-associated disease, find markers of evolution, and above all explore the efficacy of targeted therapies to test primate-restricted molecules.

Original languageEnglish
Article number244
Number of pages14
JournalJournal of neuroinflammation
Volume16
Issue number1
DOIs
Publication statusPublished - 30-Nov-2019

Keywords

  • Anti-MOG IgG
  • Cytokines
  • Complement
  • Demyelination
  • Brain inflammation
  • CSF
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • MYELIN OLIGODENDROCYTE GLYCOPROTEIN
  • MULTIPLE-SCLEROSIS
  • ANTIBODIES
  • MODELS
  • EAE

Cite this