Abstract Details

Title Neuronal uptake, antibody binding, and injury by anti-Ma2 antibodies in organotypic culture of rat brain: a possible role for anti-Ma2 antibody in production of neurological disease

Topic Autoimmune Neurology

Presentation(s) Autoimmune Neurology Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 029

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

Background 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 neurological 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.

Design/Methods Organotypic culture of rat hippocampus, brainstem, and cerebellar were incubated with serum or cerebrospinal fluid (CSF) from 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. Culture were then fixed, permeabilized, stained with Cy-5 conjugate anti-human IgG, and studied using confocal microscopy.

Results 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 structure label 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 the time studied. Uptake of anti-Ma2 by Purkinje or other cerebellar neurons was rarely observed.

Conclusions 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 plan a direct role in neuronal injury.

Authors/Disclosures
Jonathan R. Galli, MD (University of Utah) PRESENTER	Dr. Galli has nothing to disclose.
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.
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.

��ɫ��

��ɫ��