Antibodies to covalent aggregates of insulin in blood of insulin-using diabetic patients.
A covalent aggregate twice the size of insulin accounts for approximately 28% of total circulating insulin immunoreactivity in type I diabetic patients. These aggregates are probably covalent dimers of insulin and should contain unique epitopes distinct from the parent molecule. Therapeutic insulin contains a similar material and is the source of the circulating aggregate. Anti-aggregate antibodies were detected by binding-inhibition techniques in 9 of 29 long-term diabetic patients. These antibodies were directed against structures distinct from those of the parent molecule insulin monomer. All antibody-positive patients were men whose blood also contained antibodies to insulin monomer. We conclude that the blood of approximately 30% of insulin-using diabetic patients contains antibodies directed against epitopes unique to the insulin aggregates. Because insulin monomer and aggregates probably share a common primary amino acid sequence, the anti-aggregate antibodies are probably directed against conformational determinants. Further work is needed to determine whether such aggregates promote or accentuate the development of anti-insulin antibodies in certain genetically predisposed individuals.
D000328:Adult; D000906:Antibodies / Q000032:analysis*; D000937:Antigen-Antibody Reactions; D055598:Chemical Phenomena; D002621:Chemistry; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007328:Insulin / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011108:Polymers / Q000276:immunology; D011487:Protein Conformation
D000906:Antibodies; D000939:Epitopes; D007328:Insulin; D011108:Polymers