Insulin antibodies: reduction in various anti-insulin IgG subclasses with human insulin therapy.
The insulin-induced antibodies decrease on substitution of bovine-porcine with human insulin. In order to test whether there is a preferential reduction of certain anti-insulin IgG subclass, we investigated the composition of insulin antibodies. In serum samples collected from 23 bovine-porcine insulin-treated patients with clinical manifestations of insulin-induced immune problems (12 insulin resistant cases, 11 with lipodystrophy and/or local insulin allergy), the amounts of 125I-bovine insulin bound with IgG1, IgG2, IgG3 and IgG4 subclasses were 27.0 +/- 4.7, 7.8 +/- 2.3, 39.0 +/- 11.6 and 55.1 +/- 10.9 ng/ml respectively. Thus, there was an abundance of insulin antibodies of IgG4 subclass, and a relative paucity of IgG2. When the bovine-porcine insulin was changed to rDNA human insulin in 15 patients, the total insulin-binding IgG antibodies decreased by 58.6% with concomitant reductions in IgG1 (from 26.7 +/- 6.6 to 16 +/- 5.3), IgG3 (from 5.9 +/- 3.1 to 4.3 +/- 2.1), and IgG4 (from 46.4 +/- 15.6 to 18.4 +/- 7.9 ng of insulin bound/ml) subclasses. These observations suggest that in a selected subset of patients with insulin-induced immune problems, the bovine-porcine insulin induces antibodies of all four IgG subclasses but the IgG4 response predominates. With the substitution to human insulin, a reduction in the immune stimulus occurs followed with decreases in the IgG1, IgG3 and IgG4 subclasses.
Kumar
D
D
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002417:Cattle; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006041:Goats / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology*; D007328:Insulin / Q000276:immunology / Q000627:therapeutic use*; D007330:Insulin Antibodies / Q000032:analysis / Q000276:immunology*; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D013045:Species Specificity; D013552:Swine
D007074:Immunoglobulin G; D007328:Insulin; D007330:Insulin Antibodies; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins