@article {Whitney7307, author = {Karl D. Whitney and James O. McNamara}, title = {GluR3 Autoantibodies Destroy Neural Cells in a Complement-Dependent Manner Modulated by Complement Regulatory Proteins}, volume = {20}, number = {19}, pages = {7307--7316}, year = {2000}, doi = {10.1523/JNEUROSCI.20-19-07307.2000}, publisher = {Society for Neuroscience}, abstract = {GluR3 autoantibodies have been implicated in the development of Rasmussen{\textquoteright}s encephalitis, a rare neurodegenerative disease of humans characterized by epilepsy and degeneration of a single cerebral hemisphere. GluR3 autoantibodies are found in some Rasmussen{\textquoteright}s encephalitis patients, and GluR3 antibodies raised in rabbits destroy cultured cortical cells in a complement-dependent manner. In this study, the cellular targets of anti-GluR3 antisera-mediated cytotoxicity were examined in mixed primary neuronal{\textendash}glial cultures of rat cortex. Unexpectedly, astrocytes were the principal target of the cytotoxic effects as assessed by immunohistochemistry and lactate dehydrogenase activity; neurons were destroyed to a lesser extent. Astrocyte vulnerability was rescued by transfection with complement regulatory proteins, and neuronal resistance was defeated by impairing complement regulatory protein function. Astrocyte death may occur in Rasmussen{\textquoteright}s encephalitis, and destruction of this cell type may play a critical role in the progression of this disorder. The present findings suggest complement regulatory protein expression may in part determine the nature and severity of Rasmussen{\textquoteright}s encephalitis and other complement-dependent nervous system diseases and thus underscore the need for a systematic investigation of the expression of all known complement regulatory proteins in healthy and diseased nervous system tissues.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/20/19/7307}, eprint = {https://www.jneurosci.org/content/20/19/7307.full.pdf}, journal = {Journal of Neuroscience} }