Clinical and immunohistochemical comparison of in vivo injected anti‐Hu and control IgG in the nervous system of the mouse

Anti-Hu antibodies are usually present in patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN), and anti-Hu IgG is found in the nucleus of neurons in the autopsy of these patients. To investigate the clinical effect and distribution of anti-Hu IgG in the nervous system in an experimental animal model, we injected intraperitoneally anti-Hu IgG from five patients with PEM/SN to mice daily for 1 or 2 weeks. The IgG distribution in the nervous system was analyzed by an avidin-biotin immunoperoxidase technique in animals sacrificed 24 h after the last injection. In one group of mice the nervous system was fixed by perfusion and in another (autopsy group) by immersion after keeping the dead animal 16 h at 4°C. None of the mice showed clinical or pathological abnormalities. IgG immunoreactivity was similar in the nervous system of mice injected with anti-Hu or control IgG. In the perfusion-fixed mice, IgG was present in leptomeninges, choroid plexus and extracellular space of Gasserian and dorsal root ganglia (DRG). In the autopsy group, there was IgG immunoreactivity in the cytoplasm of neurons of many areas of the brain and in more than 90% of neurons of DRG. Neuronal nuclear IgG deposits were only rarely observed. We conclude that anti-Hu antibodies alone probably are not responsible for the PEM/SN syndrome. IgG diffusion into the cytoplasm of neurons is a post-mortem artifact, but this model did not reproduce the predominant nuclear IgG staining observed in autopsies from PEM/SN patients.