The online version of this article (doi:10.1186/s12974-017-0899-1) contains supplementary material, which is available to authorized users.
Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized.
The objective of this study is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology.
Purified IgG2a monoclonal anti-MOG antibody and mouse complement were stereotactically injected into the corpus callosum of wild-type and type I IFN receptor deficient mice (IFNAR1-KO) with and without pre-established experimental autoimmune encephalomyelitis (EAE).
Anti-MOG induced complement-dependent demyelination in the corpus callosum of wild-type mice and did not occur in mice that received control IgG2a. Deposition of activated complement coincided with demyelination, and this was significantly reduced in IFNAR1-KO mice. Co-injection of anti-MOG and complement at onset of symptoms of EAE induced similar levels of callosal demyelination in wild-type and IFNAR1-KO mice.
Anti-MOG antibody and complement was sufficient to induce callosal demyelination, and pathology was dependent on type I IFN. Induction of EAE in IFNAR1-KO mice overcame the dependence on type I IFN for anti-MOG and complement-mediated demyelination.
Additional file 1: H&E and LFB staining of spinal cord sections from PBS- and anti-MOG + C-treated C57BL/6 and IFNAR1-KO mice with EAE. Shown is dorsal horn of the lumbar spinal cord taken 2 days post-intra-CC injection. There was no significant difference in EAE severity between IFNAR1-KO and C57BL/6 mice. EAE severity was 2.2 ± 0.2 and 3.2 ± 0.6 for C57BL/6 mice injected with PBS and anti-MOG + C, respectively, and 2.3 ± 0.2 and 3.0 ± 0.4 for IFNAR1-KO injected with PBS and anti-MOG + C, respectively. H&E and LFB magnification: ×4 and ×20. (JPEG 375 kb)12974_2017_899_MOESM1_ESM.jpeg
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- Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination
Carsten Tue Berg
- BioMed Central
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