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Abstract Details

Neuronal uptake, antibody binding, and injury by anti-Ma2 antibodies in organotypic cultures of rat brain: a possible role for anti-Ma2 antibody in production of neurological disease
Autoimmune Neurology
P6 - Poster Session 6 (12:00 PM-1:00 PM)
15-012

Anti-Ma2 antibodies are paraneoplastic autoantibodies associated with syndromes of limbic, diencephalic, and brainstem encephalitis in patients with testicular or other neoplasms.  The role of anti-Ma2 antibodies in neuronal injury has not been defined, nor is it known whether these antibodies interact with their intracellular antigenic targets in living neurons.  We have previously demonstrated that both anti-Yo and anti-Hu antibodies are taken up by neurons in rat organotypic brain cultures and that intracellular binding of these antibodies is followed by cell death.  Here we examined whether neuronal uptake and cytotoxicity of anti-Ma2 antibodies in vitro affected brain regions involved in clinical disease.

To determine the effect of paraneoplastic anti-Ma2 antibodies on neurons in organotypic rat brain cultures.

Organotypic cultures of rat hippocampus, brainstem and cerebellum, were incubated with sera or cerebrospinal fluid (CSF) from 5 anti-Ma2 positive patients for intervals of up to 144 hours.  Dispersed cortical neuronal cultures were also studied.  Neuronal viability was determined using SYTOX dead cell staining.  Cultures were then fixed, permeabilized, stained with Cy-5 conjugated anti-human IgG, and studied using confocal microscopy.

Anti-Ma2 antibodies were taken up by neurons in hippocampus and brainstem and accumulated in cytoplasm, nuclei, and granular structures in both cytoplasm and neuronal processes.  A fraction of the granular structures labeled with anti-Ma2 antibodies co-labeled with antibodies to the RNA-binding protein, Staufen.  Antibody uptake was associated with scattered neuronal death over the period of time studied.  Uptake of anti-Ma2 by Purkinje or other cerebellar neurons was rarely observed. 

Anti-Ma2 antibody was taken up by neurons in hippocampus and brainstem, followed by scattered neuronal death.  The distribution of antibody uptake and neuronal injury differed from that seen with anti-Yo and anti-Hu antibodies and corresponded to the syndromes of clinical illness seen in human patients.  Anti-Ma2 antibody may play a direct role in neuronal injury.

Authors/Disclosures
Jonathan Ross Galli, MD (University of Utah)
PRESENTER
Dr. Galli has nothing to disclose.
Kenneth E. Hill No disclosure on file
Susan Clawson No disclosure on file
Blair Wood No disclosure on file
Stacey Clardy, MD, PhD, FAAN (University of Utah) Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca/Alexion. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen/Horizon. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from NIH/NINDS. The institution of Dr. Clardy has received research support from SRNA. The institution of Dr. Clardy has received research support from Alexion/AstraZeneca. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel/Lodging/Honoraria with U of Iowa, Miami, Stanford, Barrow, Beaumont Health, CCF, Emory.
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 E. Greenlee, MD, FAAN (University of Utah) 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.