Autoimmunity to neuronal antigens in multiple sclerosis

Axonal damage is considered as the major cause of chronic disability in MS but the underlying pathological mechanisms are poorly understood. Similar to immune-mediated myelin destruction, autoimmunity to neuronal/axonal antigens may play an important role in axonal damage. T cell responses to neuronal antigens are observed in MS as well as in healthy controls indicating that such responses are part of the immune repertoire. Whether specific differences between responses in MS and controls differ is not known. Likewise, antibodies to neuronal and axonal antigens are observed in a range of diseases and healthy controls although higher responses correlate with the degree of neurodegeneration. That such antibodies play a role in disease comes from animal studies. Anti-axonal antibodies are pathogenic in animals and induce axonal damage. To model spasticity as observed in MS, immunisation of animals with neuronal antigens has been shown to induces neuronal and axonal damage and grey matter lesions along with clinical signs of neurological degeneration. Furthermore, immunoglobulin deposits are observed inside neurons and axons in these animals. Clearly auto-autoimmunity to axonal antigens plays an important role in mediating the axonal damage in animals indicting that such responses in MS may also be pathogenic merely than acting as a surrogate marker for axonal degeneration.