Lymphocyte proliferation as a test of the immune response to insulin in diabetics.

Twenty-three insulin-treated diabetic patients were studied using the lymphocyte transformation test to assess insulin immunogenicity. All were known to have circulating Ig class antibodies to insulin. Thirteen subjects had a positive transformation response to either pork or beef insulin (9 to both). There was no significant correlation between the lymphocyte response and the antibody titre (r = 0.22 beef insulin and 0.12 pork insulin). The lymphocyte responses to pork and beef insulins were associated (r = 0.78) as were the antibody levels as assessed by serum binding of labelled pork and beef insulins (r = 0.86). Age, duration of diabetes, insulin dose and insulin preparation used showed no association with the lymphocyte response or the insulin antibody titre. Two subjects manifested a negative lymphocyte response to porcine insulin (2 ZN) with strongly positive response to zinc-free porcine insulin; this suggests that immunogenic determinants may reside in physical characteristics of the insulin molecule rather than in the amino acid sequence.