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J Neuroinflammation. 2019 Nov 30;16(1):244. doi: 10.1186/s12974-019-1637-7.

Anti-MOG autoantibodies pathogenicity in children and macaques demyelinating diseases.

Author information

1
Commissariat à l'Energie Atomique (CEA), Institut de biologie François Jacob, Molecular Imaging Research Center (MIRCen), 92265, Fontenay-aux-Roses, France. che.serguera-y-lagache@inserm.fr.
2
Institut national de la santé et de la recherche médicale (INSERM), MIRCen, UMS 27, 92265, Fontenay-aux-Roses, France. che.serguera-y-lagache@inserm.fr.
3
Asfalia Biologics, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France. che.serguera-y-lagache@inserm.fr.
4
Commissariat à l'Energie Atomique (CEA), Institut de biologie François Jacob, Molecular Imaging Research Center (MIRCen), 92265, Fontenay-aux-Roses, France.
5
Institut national de la santé et de la recherche médicale (INSERM), MIRCen, UMS 27, 92265, Fontenay-aux-Roses, France.
6
Asfalia Biologics, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
7
CEA, Inserm UMR 1184 and Institut de biologie François Jacob, Infectious Diseases Models for Innovative Therapies (IDMIT), Université Paris-Sud, 92265, Fontenay-aux-Roses, France.
8
Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Pediatric Neurology Department, National Referral Center for Rare Inflammatory Brain and Spinal Diseases, Hôpitaux Universitaires Paris-Sud, Paris, France.
9
Hôpital Neurologique Pierre Wertheimer, Service de Neurologie, Sclérose en plaques, pathologies de la myéline et neuro-inflammation, CHU de Lyon, 69677, Bron Cedex, France.
10
Immunology Department AP-HP, Hôpitaux Universitaires Paris-Sud, Le Kremlin Bicêtre, France.
11
Department of Immunobiology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands.
12
Department Biomedial Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands.
13
CHU Grenoble-Alpes - TIMC UMR CNRS 5525, Grenoble, France.
14
Lab. de Neuropathologie, GHU Paris-Sud - Hopital Bicêtre, 94270, Le Kremlin Bicêtre, France.

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.

KEYWORDS:

Anti-MOG IgG; Brain inflammation; CSF; Complement; Cytokines; Demyelination

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