The GM2-1 islet ganglioside has been sequenced, found to be a novel ganglioside 
structure with a sialic acid moiety in the terminal position and two residues of 
non-acetylated galactosamine and also shown to be a target of autoantibodies in 
a subset of ICA+ relatives of type 1 diabetic patients who subsequently 
progressed to the overt disease. In the present study we determined whether 
antibodies to GM2-1 or to other pancreatic gangliosides (a) are also expressed 
at disease onset and (b) are correlated with other diabetes-associated 
autoantibodies. Pancreatic gangliosides were extracted from human pancreas and 
purified by thin layer chromatography (TLC). Anti-ganglioside autoantibodies 
were determined using an indirect immunoperoxidase technique performed directly 
on TLC plates in the following groups of patients: (a) newly diagnosed type 1 
diabetic subjects before insulin therapy (n = 45); all were tested for GAD65 
autoantibodies in a fluid-phase RIA using 35S-methionine-labelled recombinant 
human GAD65. Of these patients, 24 were also tested for insulin autoantibodies 
(IAA) by a competitive fluid phase radioimmunoassay and 21 were tested for GAD67 
reactivity. (b) Forty-two age- and sex-matched normal control subjects. 
Autoantibodies to GM2-1, but not to other pancreatic gangliosides (GM3, GD3, 
GD1a), were expressed in 31 of 45 new-onset type 1 diabetic subjects and in one 
of 42 normal controls (P < 0.01), while anti-GAD65, IAA and anti-GAD67 were 
found in 31 of 45, 12 of 24 and three of 21 patients respectively, but not in 
the control group of subjects. Interestingly, occurrence of GM2-1 autoantibodies 
was significantly correlated (P < 0.005) with positivity for GAD65 
autoantibodies, but not for IAA or GAD67 autoantibodies. It is of note that both 
GAD and gangliosides are mainly expressed in islets and in neuronal tissues and, 
therefore, type 1 diabetes may be regarded as a neuroendocrine autoimmune 
disease.