WHICH GLYCOLIPIDS ARE THE AUTOANTIGENS OF CYTOPLASMATIC ISLET CELL ANTIBODIES

It has been suggested that acidic glycolipids may be the target of autoimmune phenomena in type 1 diabetes. The aim of the present study was to provide a better understanding of the nature and the chemical structure of pancreatic glycolipids reacting with antibodies from type 1 diabetic patients. Gangliosides and other acidic glycolipids were extracted from human pancreas in chloroform-methanol water and separated on fractogel TSK DEAE columns. Separated glycolipids were tested for their ability to block islet cell antibody (ICA) binding on frozen pancreatic sections. Furthermore, pancreatic acidic glycolipids and standard gangliosides and sulphatides were used as the substrate for immunostaining on thin layer chromatography (TLC) plates, using ICA-positive and ICA-negative sera. ICA binding was blocked by pancreatic acidic glycolipids even though the alkali treated lipid extract pointed to the alkali-stable acidic glycolipid character of the molecules involved in the blocking effect. ICA+ sera specifically reacted on TLC plates with two pancreatic acidic glycolipids, one migrating with the solvent front and the other with a mobility between GM2 and GM1 standards. None of the ICA-positive sera reacted with standard gangliosides (3'-LM1, 3'-isoLM1, GM1, GD1a, GD1b, GT1b). In addition, ICA+ sera reacted with different standard sulphated glycolipids. In conclusion, our results suggest that not only gangliosides, but also sulphatides, are targets of type 1 diabetes-associated antibodies.