title: Immunologic analysis of anaphylaxis to protamine component in neutral protamine Hagedorn human insulin.
abstract: We report the clinical and immunologic analysis of two patients with diabetes who had anaphylaxis to neutral protamine Hagedorn (NPH) human insulin in the absence of allergy to regular insulin. A 36-year-old woman without a recent history of local insulin reactions or interruption of insulin therapy experienced anaphylaxis within 15 minutes of her usual morning dose of subcutaneously administered NPH human insulin. A 62-year-old man with a history of generalized reactions to NPH human insulin and of anaphylaxis to intravenously administered protamine had generalized urticaria after injection of NPH human insulin. Both patients subsequently tolerated Lente human insulin. Skin test results in both patients were negative to regular and Lente insulin preparations but 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 insulin, and that their IgE antibodies to protamine recognized protamine antigenic determinants in NPH human insulin. We conclude that the anaphylactic reactions to NPH insulin in our patients were mediated by IgE to protamine, which should be a pathogenetic consideration in the evaluation of immediate-type reactions to protamine-containing insulins.
authors.affiliation: Department of Internal Medicine, Saint Louis University School of Medicine, MO 63104-1028.
authors.forename: M S
authors.initials: MS
authors.lastname: Dykewicz
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: N
authors.initials: N
authors.lastname: Orfan
authors.forename: T J
authors.initials: TJ
authors.lastname: Yoo
authors.forename: P
authors.initials: P
authors.lastname: Lieberman
mesh_terms: D000328:Adult; D000707:Anaphylaxis / Q000139:chemically induced*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007328:Insulin / Q000276:immunology; D007336:Insulin, Isophane / Q000009:adverse effects* / Q000737:chemistry* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011479:Protamines / Q000009:adverse effects* / Q000276:immunology; D011852:Radioallergosorbent Test; D012882:Skin Tests
chemical_list: D007074:Immunoglobulin G; D007328:Insulin; D011479:Protamines; D007073:Immunoglobulin E; D007336:Insulin, Isophane