Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain

Abstract

IntroductionAntibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) are present in some neuromyelitis optica patients who lack antibodies against aquaporin-4 (AQP4-IgG). The effects of neuromyelitis optica MOG-IgG in the central nervous system have not been investigated in vivo. We microinjected MOG-IgG, obtained from patients with neuromyelitis optica, into mouse brains and compared the results with AQP4-IgG.ResultsMOG-IgG caused myelin changes and altered the expression of axonal proteins that are essential for action potential firing, but did not produce inflammation, axonal loss, neuronal or astrocyte death. These changes were independent of complement and recovered within two weeks. By contrast, AQP4-IgG produced complement-mediated myelin loss, neuronal and astrocyte death with limited recovery at two weeks.ConclusionsThese differences mirror the better outcomes for MOG-IgG compared with AQP4-IgG patients and raise the possibility that MOG-IgG contributes to pathology in some neuromyelitis optica patients.

Antibodies to myelin oligodendrocyte glycoprotein in aquaporin 4 antibody seronegative longitudinally extensive transverse myelitis: Clinical and prognostic implications

“…Indeed, the intracerebral injection of human MOG-ab in mice causes only few and transient myelin changes and alteration of axonal protein expression without leukocyte infiltration, and recovery within two weeks. 25 In the present study, four MOG-ab positive patients fulfilled the current criteria for clinical NMO. 1 Some studies have reported that NMOSD patients show distinctive clinical findings depending on the underlying biological profile (MOG vs AQP4 autoimmune phenotype).…”

Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein

“…The transient nature of MRI findings has been previously noted in individual patients with autoimmune diseases and MOG antibodies 11. Interestingly, Saadoun et al23 recently showed in a mouse model that intraparenchymal injected MOG antibodies induced lesions, which were transient and not associated with complement activation or recruitment of inflammatory cells in the rodent brain.…”

Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review

“…Experiments performed with injected IgG in mouse brain demonstrated that anti-MOG IgG antibodies cause myelin changes and alter the expression of axonal proteins but do not produce axonal loss, inflammation, neuronal or astrocyte death, with recovery within two weeks. On the other hand, anti-AQP4 IgG antibodies produce complement-mediated myelin loss, and astrocyte and neuronal death with limited recovery at two weeks [85]. Seronegative patients for anti-AQP4 and positive for anti-MOG seem to have more favorable clinical prognosis [86].…”