Studies on autoimmunity for initiation of beta-cell destruction. VIII. Pancreatic beta-cell dependent autoantibody to a 38 kilodalton protein precedes the clinical onset of diabetes in BB rats.
Autoantibody to a rat islet cell-protein of 38 kilodalton was detectable at around 30 days of age in the sera of diabetes-prone Biobreeding (DP-BB) rats by both immunoprecipitation and differential Western blotting methods. Anti-38 kilodalton islet cell autoantibody was not, however, observed in the sera from 5- to 20-day-old DP-BB rats. Over 90% of DP-BB rats in which the antibody was detected, eventually developed Type 1 (insulin-dependent) diabetes mellitus. The antibody disappeared within 2 weeks after diabetes onset. However, it was preserved in the sera of DP-BB rats which had been treated with silica to prevent insulitis. The anti-38 kilodalton islet cell autoantibody was not detected in sera from control Wistar Furth (WF) rats. The autoantibody also cross-reacted with a rat insulinoma (RINm5F) cell protein of 38 kilodalton, but did not react with protein from mouse fibroblast (L-929 cells), rat pituitary cells (GH3 cells), or normal rat lymphocytes. The production of the autoantibody appears to be pancreatic Beta-cell dependent, since the autoantibody disappears after almost complete depletion of Beta cells, but is consistently present as long as Beta cells remain. Identification of the Beta-cell dependent anti-38 kilodalton islet cell autoantibody, which cross-reacts with a rat insulinoma cell protein of 38 kilodalton and precedes the onset of Type 1 diabetes in BB rats, will be invaluable for study of the molecular nature of a target islet cell autoantigen associated with the induction of autoimmunity in DP-BB rats.
Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre, Calgary, Alberta, Canada.
I Y
IY
Ko
S H
SH
Ihm
J W
JW
Yoon
D000818:Animals; D000941:Antigens / Q000032:analysis* / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D015153:Blotting, Western; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007340:Insulinoma; D007515:Islets of Langerhans / Q000276:immunology*; D008970:Molecular Weight; D010190:Pancreatic Neoplasms; D011236:Prediabetic State / Q000276:immunology*; D051381:Rats; D011913:Rats, Inbred BB; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011920:Rats, Inbred WF
D000941:Antigens; D001323:Autoantibodies