Abstract Details

Anti-Yo and anti-Hu are autoantibodies associated with syndromes of paraneoplastic neuronal destruction in the setting of gynecological or breast carcinomas (anti-Yo) or small cell lung cancer (anti-Hu).  The roles of these two antibodies in causing neuronal death is uncertain: although both antibodies have been shown to cause neuronal death in rodent brain slice cultures, production of neuronal death by these antibodies has never been demonstrated in living animals.

1) To determine whether anti-Yo and anti-Hu antibodies are taken up by neurons and cause neuronal death in living animals, as has been shown to occur in rodent brain slice cultures.  2) To determine whether methods of detecting neuronal death in slice culture can be used to study brains of animals following antibody infusion.

Mice were injected intraventricularly with anti-Hu antibodies and sacrificed at 72 hours.  In subsequent studies, mice were implanted with Alzet osmotic pumps and infused intraventricularly with anti-Yo or anti-Hu antibodies over a period of 2 weeks.  Cerebellar slice cultures prepared from brains of treated and control animals were incubated with SYTOX dyes to detect cell death, fixed, and labeled with Cy5-conjugated anti-human IgG to detect antibody uptake.

Neuronal uptake of anti-Hu antibodies was demonstrated in slice cultures prepared from animals injected intraventricularly.  Uptake of both anti-Yo and anti-Hu antibodies was demonstrated in animals infused using Alzet pumps.  In both sets of experiments, antibody uptake was accompanied by focal neuronal death as indicated by staining with SYTOX dyes.

Anti-Hu and anti-Yo antibodies can be taken up by neurons in living animals, as has been previously demonstrated in rodent brain slice cultures.  Both antibodies can cause neuronal death without immunization to induce a specific T cell response.  These findings support a direct role for anti-Yo and anti-Hu antibodies in causing paraneoplastic neuronal injury.