Gangliosides act as onconeural antigens in paraneoplastic neuropathies.
We describe two patients with progressive neuropathy and lung cancer in whom gangliosides (GS) may represent the oncoantigens. Patient 1 had motor neuropathy, high titers of IgG1 and IgG3 to GD1a and GM1, and expansion of circulating gamma-delta T lymphocytes, a T-cell subset responding to glycolipids. Patient 2 presented with Miller-Fisher-like syndrome and IgG3 activity to disialo-GS. In both cases, decreased autoimmune responses and stabilization of neuropathy were accomplished by tumor treatment. By immunohistochemistry, patient 1's IgG bound to his own tumor and to structures of normal nervous system expressing GD1a or GM1. Infiltration of IgG in the same neural structures was found at his autopsy. Regarding cellular immunity, the proportion of gamma-delta T lymphocytes infiltrating carcinoma from patient 1 was significantly higher than in neoplastic controls. These results indicate that GS may represent onconeural antigens in paraneoplastic neuropathy (PNN); their expression on neoplastic tissue may elicit autoimmune responses, which also target neural structures.
Institute of Neurology, Azienda Ospedaliera of Verona, P. Scuro, 37134 Verona, Italy.
Luca
L
De Toni
Silvia
S
Marconi
Ettore
E
Nardelli
Daniela
D
Alberti
Giovanna
G
Borsellino
Giulio
G
Fracasso
Simona
S
Bach
Laura
L
Bertolasi
Antonio
A
Santo
Antonella
A
Bassi
Daniela
D
Tramonti
Luca
L
Battistini
Bruno
B
Bonetti
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000276:immunology* / Q000378:metabolism; D020364:Paraneoplastic Polyneuropathy / Q000276:immunology* / Q000378:metabolism*
D000951:Antigens, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; D005732:Gangliosides