MOG-induced experimental autoimmune encephalomyelitis in the rat species triggers anti-neurofascin antibody response that is genetically regulated

Flytzani, S., Guerreiro-Cacais, A. O., N’diaye, M., Lindner, M., Linington, C. , Meinl, E., Stridh, P., Jagodic, M. and Olsson, T. (2015) MOG-induced experimental autoimmune encephalomyelitis in the rat species triggers anti-neurofascin antibody response that is genetically regulated. Journal of Neuroinflammation, 12, 194. (doi: 10.1186/s12974-015-0417-2) (PMID:26511327) (PMCID:PMC4625640)

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Abstract

Background Ιn multiple sclerosis (MS), axonal damage leads to permanent neurological disabilities and the spreading of the autoimmune response to axonal antigens is implicated in disease progression. Experimental autoimmune encephalomyelitis (EAE) provides an animal model that mimics MS. Using different EAE models, we investigated the pathophysiological basis of epitope spreading to neurofascin, a protein localized at the node of Ranvier and its regulation by non-MHC genes. Methods We used two different EAE models in DA rat; one which is induced with myelin oligodendrocyte glycoprotein (MOG) which leads to disease characterized by profound demyelination, and the second which is induced with myelin basic protein (MBP) peptide 63–88 which results in severe central nervous system (CNS) inflammation but little or no demyelination. We determined anti-neurofascin antibody levels during the course of disease. Furthermore, the anti-neurofascin IgG response was correlated with clinical parameters in 333 (DAxPVG.1AV1) x DA rats on which we performed linkage analysis to determine if epitope spreading to neurofascin was affected by non-MHC genes. Results Spreading of the antibody response to neurofascin occurred in demyelinating MOG-induced EAE but not in EAE induced with MBP peptide 63–88. Anti-neurofascin IgG levels correlated with disease severity in (DAxPVG.1AV1) x DA rats, and a genomic region on chromosome 3 was found to influence this response. Conclusions Inter-molecular epitope spreading to neurofascin correlates with disease severity in MOG-EAE is dependent on extensive demyelination and is influenced by non-MHC genes. The findings presented here may shed light on factors involved in the severity of MS and its genetics.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lindner, Dr Maren and Linington, Professor Christopher
Authors: Flytzani, S., Guerreiro-Cacais, A. O., N’diaye, M., Lindner, M., Linington, C., Meinl, E., Stridh, P., Jagodic, M., and Olsson, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Neuroinflammation
Publisher:BioMed Central Ltd
ISSN:1742-2094
ISSN (Online):1742-2094
Copyright Holders:Copyright © 2015 Flytzani et al.
First Published:First published in Journal of Neuroinflammation 12:194
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
515251EuratransAnna DominiczakEuropean Commission (EC)241504RI CARDIOVASCULAR & MEDICAL SCIENCES