Insulin Antibodies: Reduction in Various Anti-Insulin IgG Subclasses with Human Insulin Therapy

Summary

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.

Key words

Insulin Antibodies - IgG Subclass - Human Insulin - Immune Complication - Allergy - Lipoatrophy - Porcine Insulin - Bovine Insulin