Year: 2000
Type: article
Abstract: In 1973, the serendipitous development at the Salk Institute of a myasthenic-like syndrome in rabbits immunized with acetylcholine receptors opened the door to the understanding of myasthenia gravis, the first neurological disorder for which an autoantibody-mediated autoimmune pathogenesis has been proven. History often repeats itself, and twenty years or so later, virtually identical circumstances led to the search and identification, again in the same Neurobiology Department at the Salk Institute, of the first potentially pathogenic autoantibodies in a neuronal disorder of the CNS. The unexpected onset of seizures and the presence of patchy cortical microglial nodules and lymphocytic infiltrates in two out of three rabbits immunized with recombinant glutamate receptor 3 (GluR3) prompted the search and discovery of anti-GluR3 autoantibodies in patients with Rasmussen's encephalitis (RE) (Rogers et al. 1994). RE is a rare pediatric encephalopathy in which the continuous occurrence of untreatable seizures in a single cerebral hemisphere progressively leads to hemiplegia and dementia (Oguni et al. 1991). The hypothesis that RE has a humoral autoimmune pathogenesis has been corroborated by the partial, although transitory, improvement of several RE patients following plasmapheresis (Rogers et al. 1994) or the selective removal of circulating immunoglobulins by protein A chromatography (Antozzi et al. 1998). It was proposed that the anti-GluR3 autoantibodies act as receptor agonists and thus induce neuronal death by an excitotoxic mechanism (Twyman et al. 1995). In a following study, it was shown that the death of cultured rat cortical neurons incubated with rabbit anti-GluR3 IgG is complement dependent (He et al. 1998). Whether excitoxicity and complement-mediated cell death contribute equally to the pathogenesis of RE remains an open question.
Source: Neuron
Authors: Michele Solimena, Pietro De Camilli
Institutions: Yale University, Howard Hughes Medical Institute
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
OpenAlex ID: W1965512160