Skip to main content

CNS autoimmunity mediated by pathogenic T cell and antibody responses: immunogenetics, pathogenesis and therapy of MOG-induced EAE

Article Category

Article available in the folowing languages:

New insights in multiple sclerosis etiology

Multiple Sclerosis (MS) is the most inflammatory demyelinating disease of the central nervous system in Europe. A group of research institutes introduced new concepts on the possible causes of MS, based on observations made on an animal model.

Health

Myelin is an insulating sheath that surrounds nerve fibres. The main feature of MS is the loss of myelin, known as demyelination, due to attack of the sheath by inflammatory cells. In northern Europe and North America this illness is a major cause of chronic disability in young and middle-aged adults. However, the etiology of MS is unknown and there is no satisfactory treatment available. Research supports that MS is an autoimmune disease, which is triggered in genetically susceptible individuals by environmental agents that disrupt self-tolerance to myelin autoantigens ("self" proteins normally recognisable by one's own system). One potential target for the pathogenic response is the myelin oligodendrocyte glycoprotein (MOG), which is a minor component of the central nervous system (CNS). The autoimmune disorder is associated with the selective activation and expansion of the T cell population, which leads to host tissue destruction. However, identification of the most important inflammatory cell type and/or mediator has proven difficult and findings are controversial. A group of research institutes made studies in order to identify the genetic loci that determine susceptibility to MS and their links with potential environmental factors. Their approach was based on an animal model of MS, known as experimental autoimmune encephalomyelitis (EAE). The animals are injected with MOG protein, inducing an autoimmune response. In this way the animal's immune system mounts an attack on its own myelin, closely resembling MS in humans. Studies demonstrated that there is a duality in the pathogenic autoimmune response to MOG, comprising of MOG-specific T and B cells, implying that successful tolerogenic and/or therapeutic strategies must efficiently control both of them. Moreover, an association between multiple sclerosis and diet, in particular the consumption of milk and milk products, was identified. The milk protein butyrophilin (BTN) has an extensive amino acid homology with MOG, providing the first experimental evidence that a component of the diet can influence the autoimmune repertoire and provide a trigger to initiate autoimmune disease.

Discover other articles in the same domain of application