IMMUNOLOGICAL ANALYSIS OF ANAPHYLAXIS TO PROTAMINE COMPONENT IN NEUTRAL PROTAMINE HAGEDORN HUMAN INSULIN

We report the clinical and immunologic analysis of two patients with d iabetes who had anaphylaxis to neutral protamine Hagedom (NPH) human i nsulin in the absence of allergy to regular insulin. A 36-year-old wom an without a recent history of local insulin reactions or interruption of insulin therapy experienced anaphylaxis within 15 minutes of her u sual morning dose of subcutaneously administered NPH human insulin. A 62-year-old man with a history of generalized reactions to NPH human i nsulin and of anaphylaxis to intravenously administered protamine had generalized urticaria after injection of NPH human insulin. Both patie nts subsequently tolerated Lente human insulin. Skin test results in b oth patients were negative to regular and Lente insulin preparations b ut positive to NPH insulin and to protamine at concentrations tested. In vitro assays demonstrated that both patients had markedly elevated serum levels of IgE and IgG to protamine, but not to regular human ins ulin, and that their IgE antibodies to protamine recognized protamine antigenic determinants in NPH human insulin. We conclude that the anap hylactic reactions to NPH insulin in our patients were mediated by IgE to protamine, which should be a pathogenetic consideration in the eva luation of immediate-type reactions to protamine-containing insulins.