Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 52

Gangliosides (Gs) have been implicated as potential antigens in autoimmune neuropathies and anti-tumoral immune response, but their role in paraneoplastic neuropathy has been poorly investigated. We describe one patient affected by lung adenocarcinoma and subacute motor axonal neuropathy with high titres of IgG1 and IgG3 to several Gs. Expansion (3% of total T cells) of peripheral g/d T lymphocytes was found, as compared to healthy controls (<0.5%) and to patients with lung neoplasia without neuropathy (1.1%). At three months after neoplasia removal, we observed stabilization of the neuropathy, decline of anti-Gs IgG and of g/d T cells, which dropped to normal values. Expression of GM1, GD1a, GM2 and GM3 was found by immunohistochemistry on patient's neoplastic cells, but not in control lung neoplasia. Absorption experiments of anti-Gs IgG revealed that only GD1a and GM1, among all Gs tested, significantly decreased anti-Gs IgG reactivity. Indirect immunohistochemistry with biotinylated IgG purified from the patient showed positive signals on motoneurons, dorsal root ganglia, axonal structures and Schwann cells and his own neoplastic cells. At autopsy, IgG deposits were found on the same neural targets. Purified IgG from the patient exerted high levels of cytotoxicity on both Schwann and neuroblastoma cells, as compared to healthy controls. The association of neoplasia, peripheral neuropathy and autoimmune responses to Gs observed in our patient proposes a pathogenetic role for Gs as putative autoantigens in paraneoplastic neuropathy.