title: Anti-peptide autoantibodies and fatal anaphylaxis in NOD mice in response to insulin self-peptides B:9-23 and B:13-23.
abstract: There is evidence that amino acids 9-23 of the insulin B chain are a major target of anti-islet autoimmunity in type 1 diabetes. Administration of this peptide to NOD mice prevents diabetes, and phase I trials of an altered peptide ligand of B:9-23 are underway in humans. We were interested in long-term subcutaneous therapeutic administration of B:9-23 without adjuvant. To our initial surprise, the peptide consistently induced fatal anaphylaxis in NOD mice after 6 weeks of administration. Anaphylaxis could be blocked by a combination of antihistamine and platelet-activating factor antagonist (but neither alone) or by a combination of anti-IgG receptor and anti-IgE antibodies. High titers of anti-B:9-23 antibodies were induced within 3-4 weeks of immunization with the peptide. Peptide B:13-23 also induced anaphylaxis and was more potent than peptide B:9-23. Antibodies induced by peptide B:9-23 and peptide B:13-23 did not cross-react with each other. Thus, the insulin peptides B:9-23 and B:13-23, even when administered subcutaneously in the absence of adjuvant, can induce a dramatic humoral response leading to fatal anaphylaxis in NOD mice.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: Liu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Taylor
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D004745:Enkephalins; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology; D007328:Insulin / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D010446:Peptide Fragments / Q000276:immunology*; D011498:Protein Precursors; D011726:Pyridinium Compounds / Q000494:pharmacology
chemical_list: D001323:Autoantibodies; D004745:Enkephalins; D007074:Immunoglobulin G; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D011726:Pyridinium Compounds; C097877:insulin B (9-23); C056943:peptide B; C053321:CV 6209; D007073:Immunoglobulin E