Autoimmunity to the GM2-1 islet ganglioside before and at the onset of type I diabetes.
Recently, the GM2-1 pancreatic islet ganglioside, proposed as a potential autoantigen in type I diabetes autoimmunity, has been biochemically characterized and found to be a novel ganglioside structure. In the present study, we aimed to determine whether an autoimmune response toward this novel islet molecule is 1) present in type I diabetes and is specifically directed against this molecule and not to gangliosides in general and 2) predictive of disease in high-risk subjects. To this end, the following patients have been studied: 1) 24 newly diagnosed type I diabetic subjects, 20 islet cell autoantibody (ICA)-negative first-degree relatives of type I diabetic subjects, and 25 age-matched normal control individuals; and 2) 31 prospectively evaluated ICA+ first-degree relatives of type I diabetic subjects who were followed for up to 10 years, during which 14 of them developed type I diabetes. A direct assay for autoantibodies to GM2-1 and to other pancreatic gangliosides (GM3, GD3, GD1a) was developed using an indirect immunoperoxidase technique performed directly on thin layer chromatography plates. Anti-GM2-1 autoantibodies (all belonging to the IgG class) were expressed in a high percentage of newly diagnosed type I diabetic subjects (71%), while no significant difference was found in the expression of antibodies directed against other pancreatic gangliosides (GM3, GD3, GD1a) among the different groups studied. Anti-GM2-1 autoantibodies were also present in ICA+ relatives (64%) (P < 0.001 vs. control subjects and ICA-relatives): in this group, life table analysis of progression to diabetes showed that anti-GM2-1 autoantibodies were significantly (P < 0.001) associated with disease, occurring in all relatives developing type I diabetes within 5 years and thus identifying a cohort of ICA+ subjects with markedly increased diabetes risk.
Dotta
F
F
Department of Endocrinology, University La Sapienza, Rome, Italy.
Gianani
R
R
Previti
M
M
Lenti
L
L
Dionisi
S
S
D'Erme
M
M
Eisenbarth
G S
GS
Di Mario
U
U
D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005190:Family; D005678:G(M2) Ganglioside / Q000276:immunology* / Q000302:isolation & purification; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000737:chemistry / Q000276:immunology*; D011236:Prediabetic State / Q000276:immunology*; D012016:Reference Values
D001323:Autoantibodies; D001324:Autoantigens; D005732:Gangliosides; D005678:G(M2) Ganglioside