Magnetic resonance imaging of experimental autoimmune encephalomyelitis in the common marmoset

Abstract

Magnetic resonance imaging (MRI) is an invaluable tool for the diagnosis and monitoring of patients with multiple sclerosis (MS) as well as for the study of the disease pathophysiology. Because of its strong clinical, radiological and histopathological similarities with the human disease, experimental autoimmune encephalomyelitis (EAE) in the common marmoset has been studied more intensively over the past several years. Here, we review the current knowledge on MRI in the marmoset EAE, and we outline the physiopathological significance and translational values of these studies with respect to MS. Accumulating evidences suggest that the application of conventional, as well as non-conventional, MRI techniques in the marmoset EAE is a promising approach to elucidate the pathological processes underlying the development of inflammatory demyelinated lesions in the central nervous system, potentially improving the identification and development of new therapeutics.

Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis

“…Relevant features in this line of research are that many biologicals developed for immunosuppressive or immunomodulatory therapy in MS cross-react between marmosets and humans and that marmosets and humans share a high level of immunological similarity. Indeed, reports from others (Maggi et al, 2017) and us documented the remarkable similarities in the afferent and effector arms between marmoset EAE and MS. The diagram in Fig.…”

“…We then asked why LCV/CalHV3 infection of B cells is important for their role as APCs in the marmoset EAE model, in particular for presentation of the vulnerable MOG34-56 peptide to pathogenic T cells. Inspired by a seminal publication from Manoury et al (2002), who first presented the concept of destructive processing of autoantigen (MBP) in thymic APCs as an explanation for why certain autoreactive T cells escape thymic selection, we proposed that this might also be the case for MOG . Our hypothesis was supported by recent studies in mice, indicating that autoreactive T cells specific for the MOG40-48 epitope escape negative thymic selection because the epitope is destroyed by a thymus-specific serine protease (TSSP), which is expressed in thymic APCs.…”

“…Hence, they will be briefly summarized. For more detail the interested reader is referred to publications from this group (see reviews by Absinta et al, 2016;Maggi et al, 2017, and references to primary publications therein).…”

“…Similar to our own studies ('t Hart et al, 1998), the study by Maggi et al (2014) revealed a substantial number of lesions without strong inflammatory activity or signs of remyelination and with moderate axonal damage, which they named late subacute lesions. Interestingly, on T2W MR images these latter lesions usually have a smaller size than the acute and subacute lesions, which may be due to the resorption of tissue edema and/or repair ('t Hart and Massacesi, 2009;Maggi et al, 2017).…”

Modelos experimentales de desmielinización-remielinización

“…En este caso se desarrollan síntomas clínicos severos hiperagudos, de forma que es un modelo que se acerca más a la variante Marburg. El Marmoset es otra especie a la que se ha inducido la EAE con diferentes procedimientos: a) por medio de un homogenado de materia blanca provocando lesiones que se parecen a las observadas en las autopsias de pacientes 26 , b) mediante la administración de glicoproteína oligodendroglial de la mielina (MOG) recombinante humana provocando lesiones desmielinizantes más pequeñas pero más duraderas 26,27 o c) mediante la inmunización con una dosis subclínica de MOG recombinante de rata seguido de una inyección de TNF␣ e interferón 27,28 . Aunque la EAE en primates se asemeja más a la enfermedad en humanos que la de los roedores en relación con los cambios patológicos, existen limitaciones tanto éticas como de coste para su uso, cuando es posible utilizar animales menores 27 .…”