Pathomechanisms of Autoantibody Production against the Nervous System

Editor’s Comment: This study is the most recent addition to the body of evidence that infections may be precipitating factors in the later development of chronic inflammation and subsequent autoimmunity in the nervous system. In a previous study performed at Queen Mary, University of London, researchers found a similar link between Epstein-Barr virus and multiple sclerosis, another neuro-degenerative autoimmune disease.

~Source: Brain Nerve. April, 2013. [Article in Japanese]

By K. Arimura

Abstract

In immune-mediated neurological disorders, the production of autoantibodies against the nervous system occurs mainly because of impaired immune tolerance. In myasthenia gravis (MG), the thymus shows pathologic alterations, particularly in anti-AChR antibody-positive patients. Further, resection of the thymus induces a clinical recovery.

The MG thymus contains all the elements, including AChR antigens, AChR-specific T cells, and antigen-secreting B cells, that are required to initiate and sustain autoantibody production. Central tolerance, established by the repertoire selection of immature T lymphocytes in the thymus, is impaired in MG patients who are positive for anti-AChR antibodies.

Recent evidence suggests that chronic inflammation elicited by viral infection is important for the production of AChR antibodies. Antibodies against ganglioside are crucial for the diagnosis of Guillain-Barre syndrome (GBS). Molecular mimicry between the lipooligosaccharides of Camplylobacter jejuni and gangliosides of the peripheral nerve causes the production of antibodies. However, less than 1 in 1000 patients infected with C. jejuni develop GBS. This fact suggests that some host factors might influence the production of antibodies. A recent hypothesis suggests that transient impairment of peripheral tolerance due to infection may play a crucial role in GBS pathogenesis.

In summary, autoantibody production might correlate with the impairment of immune tolerance as well as with innate immunity.

Source: Brain Nerve. 2013 Apr;65(4):323-32. Arimura K. Okatsu Neurology and Rehabilitation Hospital.

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