IgE antibodies to insulin and related peptides, a result of insulin treatment?

Anti-insulin immunoglobulin E (IgE) antibodies in sera of insulin-treated diabetic patients were characterized by affinity and concentration, and by binding to proinsulin and insulin A and B chains. The affinities of IgE to insulin scattered between less than 10(7) and 0.6 x 10(9) l/mol, the concentrations between 0.3 and 3.5 ng/ml. All positive sera of type 1 and few of type 2 patients recognized proinsulin, A chain, and B chain with comparable affinities and concentrations. Elevated concentrations of total serum IgE in 12 of the 16 anti-insulin IgE-positive sera from insulin-treated patients indicate that these patients are predisposed to allergies. The incidence of elevated levels of total serum IgE in type 1 (17.7%) and in type 2 (7.8%) diabetic patients did not differ from the general population. Reagins to insulin and related antigens were also observed in sera of non-diabetic allergic persons without previous contact with exogenous insulin. The natural occurrence of insulin-specific reagins makes the use of IgE as a marker of antigenicity of insulin questionable. Discrepancies between the insulin-positive radioallergosorbent test (RAST) or skin test and clinical manifestations of insulin allergy exist, because IgE antibodies with low affinities require high concentrations of insulin for binding. Such amounts of insulin may occur at the injection site, but not in the circulation.