Amyotrophic lateral sclerosis: an unconventional autoimmune disease?
The possibility of an autoimmune mechanism of pathogenesis in amyotrophic lateral sclerosis has long been considered, but the evidence to support a conventional autoimmune process, reviewed here, is inconclusive. However, antibodies that react in vitro with gangliosides have recently been found in sera of a large majority of patients with classical amyotrophic lateral sclerosis and other motor neuron syndromes. A working hypothesis is proposed, suggesting how antibodies might be related to the disease process. The hypothesis attempts to account for (1) a pathogenic role of antibodies directed against the carbohydrate components of glycolipids, (2) the selectivity of the process for motor neurons, (3) an antibody-mediated mechanism that could result in apparently degenerative neuropathological changes without signs of inflammation, and (4) a type of autoimmune response that is extremely difficult to suppress by conventional means. Although the evidence for this hypothesis is by no means complete, its critical features are all testable.
Drachman
D B
DB
Department of Neurology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
Kuncl
R W
RW
D000690:Amyotrophic Lateral Sclerosis / Q000145:classification / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D006801:Humans
D001323:Autoantibodies; D005732:Gangliosides