Anti-MOG autoantibodies pathogenicity in children and macaques demyelinating diseases

Che Serguera (1, 2, 3, 4) , Lev Stimmer (1, 4) , Claire-Maëlle Fovet (1, 2, 3, 4) , Philippe Horellou (3, 5, 6) , Vanessa Contreras (3, 5, 6) , Nicolas Tchitchek (5, 3, 6, 7) , Julie Massonneau (1, 3) , Carole Leroy (8) , Audrey Perrin (5, 3, 6) , Julien Flament (1, 3) , Philippe Hantraye (1, 3) , Joanna Demilly (1, 3) , Romain Marignier (9) , Pascale Chrétien (10) , Bert'T Hart (11, 12) , Jean Boutonnat (13, 14) , Clovis Adam (15) , Roger Le-Grand (5, 6, 3) , Kumaran Deiva (5, 6, 3, 15)

1 MIRCEN - Service MIRCEN
2 ICM - Institut du Cerveau = Paris Brain Institute
3 JACOB - Institut de Biologie François JACOB
4 CHU Pitié-Salpêtrière [AP-HP]
5 IDMIT - Infectious Diseases Models for Innovative Therapies
6 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
7 I3 - Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière]
8 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
9 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
10 GHUPS - Groupe Hospitalier Universitaire Paris-Sud
11 BPRC - Biomedical Primate Research Centre [Rijswijk]
12 UMCG - University Medical Center Groningen [Groningen]
13 TIMC - Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525
14 CHU Grenoble
15 Hôpital Bicêtre

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

Domains: Life Sciences [q-bio]

Che Serguera, Lev Stimmer, Claire-Maëlle Fovet, Philippe Horellou, Vanessa Contreras, et al.. Anti-MOG autoantibodies pathogenicity in children and macaques demyelinating diseases. Journal of Neuroinflammation, 2019, 16, pp.244. ⟨10.1186/s12974-019-1637-7⟩. ⟨cea-02397764⟩