Clinicopathological study of a myelin oligodendrocyte glycoprotein-induced demyelinating disease in LEW.1AV1 rats

Abstract

Although multiple sclerosis is considered to be an autoimmune disease in the CNS, the immune responses that take place in the CNS and lymphoid organs remain to be elucidated. Here, we have successfully induced various subtypes of experimental autoimmune encephalitis (EAE) in LEW.1AV1 rats carrying RT1(av1) on the Lewis background genes by immunization with recombinant rat myelin oligodendrocyte glycoprotein (MOG) in various solutions with adjuvants. The purpose of the present study was to analyse in more detail the clinical and immunopathological features of MOG-induced EAE in LEW.1AV1 rats. Immunization with high doses of soluble MOG with pertussis toxin induced acute, frequently fatal EAE, whereas medium doses of partially aggregated MOG without pertussis toxin produced relapsing and remitting EAE. Secondary progressive EAE was induced in some rats by immunization with the immunization protocol having an intermediate nature between the above two. The optic nerve (approximately 60% of the immunized rats) and spinal cord (100%) were frequently involved and detectable both clinically and pathologically, while there was no lesion in the cerebrum. Histological examination revealed that, despite variety in the clinical subtypes, progression of the pathological processes was strikingly uniform, i.e. initial inflammation with minimal demyelination followed by predominant demyelination with minimal lymphocyte infiltration. These findings suggest that the lesion during the later stage is maintained by humoral factors. Taken together, this experimental system can serve as a model of neuromyelitis optica. Further analysis will provide useful information to elucidate the pathogenesis and to develop immunotherapy for neuromyelitis optica and multiple sclerosis.

Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

“…In addition, the animals harbored a MOG-IgG1 directed humoral immune response [19]. Several studies demonstrated the induction of an NMO-like disease in distinct rat strains following immunization with MOG [21-23]. However, at present only limited information is available regarding MOG-IgG antibodies in human patients suffering from NMO or HR-NMO symptoms and related disorders.…”

“…Furthermore, the animals were found to exhibit highly positive serum MOG-IgG1 antibodies [19]. Additionally, there are several reports demonstrating the induction of an NMO-like disease following immunization of certain rat strains with MOG [21-23]. …”

Quantitation of myelin oligodendrocyte glycoprotein and myelin basic protein in the thymus and central nervous system and its relationship to the clinicopathologic features of autoimmune encephalomyelitis

“…LEW.1AV1 rats immunized with MOG developed relapsing‐remitting (not depicted) or secondary progressive (Fig. 1A) EAE, both of which are chronic in nature (Sakuma et al,2004). Immunization of LEW rats with MBP induced acute monophasic EAE with relatively constant onset and recovery (Fig.…”

Pertussis vaccine-induced experimental autoimmune encephalomyelitis in mice

“…However, the pertussis vaccine has been shown to be an adjuvant for the induction of a number of autoimmune diseases. In the animal model of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the Bordetella pertussis vaccine and pertussis toxin are used to increase disease incidence and severity when administered simultaneously with the autoimmune challenge [3][4][5]. It is suggested that the pro-inflammatory activity of Bordetella pertussis is mainly attributed to an increased permeabilization of the blood-brain barrier leading to an influx of immune cells into the CNS [6].…”