Abstract Details

Title Comparative Uptake and Cytotoxicity of Anti-Hu and Anti-Ri Antibodies in Rat Cerebellar Slice Cultures

Topic Neuro-oncology

Presentation(s) P02 - (-)

Poster/Presentation
Number 161

Objective

Background BACKGROUND: The paraneoplastic autoantibodies, anti-Hu and anti-Ri, recognize intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu antibody show neuronal destruction. In contrast, anti-Ri antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. The role of antibodies in causing paraneoplastic neurological injury has not been defined. However, we have previously demonstrated that anti-Yo antibodies, associated with paraneoplastic cerebellar degeneration, accumulate in Purkinje cells in slice cultures of rat cerebellum and that antibody accumulation was followed by cell death. The present study was conducted to determine 1) whether anti-Hu and anti-Ri antibodies are also taken up by neurons in this culture system; 2) whether uptake is restricted to Purkinje cells, and 3) whether uptake of either antibody is followed by cell death.

Design/Methods DESIGN/METHODS: Rat cerebellar slice cultures were incubated with either anti-Hu or anti-Ri antibodies and were followed over time. TUNEL and FLICA methods were used to detect apoptosis. The dead cell stain, SYTOX green, was used to detect non-apoptotic cell death.

Results RESULTS: Anti-Hu and anti-Ri antibodies accumulated not only in Purkinje cells but also in multiple other neuronal populations. Accumulation of anti-Hu antibody was followed by apoptosis involving multiple neuronal populations: this became detectable within 72-96 hours. In contrast, as compared to controls, cells accumulating anti-Ri antibodies showed no evidence of apoptosis or necrotic cell death over a period of 200 hours.

Conclusions CONCLUSIONS: Uptake of anti-Hu and anti-Ri antibodies was observed in viable neurons throughout the cerebellum and was not restricted to Purkinje cells. While anti-Hu antibody appears to be specifically cytotoxic, anti-Ri antibody did not affect neuronal viability and may predominantly cause neuronal dysfunction rather than death.

Authors/Disclosures
John E. Greenlee, MD, FAAN (University of Utah) PRESENTER	Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Medlink. Dr. Greenlee has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Zeigler Cohen Roche. Dr. Greenlee has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Sommers Schwartz PC. Dr. Greenlee has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for St Francis Hospital. Dr. Greenlee has received publishing royalties from a publication relating to health care. Dr. Greenlee has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Ikuo Tsunoda, PhD (Louisiana St. University Health Sci. Ctr)	No disclosure on file
Noel Carlson, PhD (VA SLC HCS)	The institution of Mr. Carlson has received research support from Biogen. Mr. Carlson has received personal compensation in the range of $100,000-$499,999 for serving as a Employee as a Researcher with Veteran Affairs.
John M. Stern, MD, FAAN	Dr. Stern has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for UCB Pharma. Dr. Stern has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for SK Life Science. Dr. Stern has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurelis. Dr. Stern has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Ceribell. Dr. Stern has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Jazz Pharma. Dr. Stern has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for LivaNova. Dr. Stern has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurelis. Dr. Stern has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for LivaNova. Dr. Stern has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sunovion. Dr. Stern has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz. Dr. Stern has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Life Sciences. Dr. Stern has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink Neurology. Dr. Stern has stock in DEARhealth. Dr. Stern has stock in Ceribell. Dr. Stern has received publishing royalties from a publication relating to health care. Dr. Stern has received publishing royalties from a publication relating to health care. Dr. Stern has received publishing royalties from a publication relating to health care. Dr. Stern has received publishing royalties from a publication relating to health care.

��ɫ��

��ɫ��