Edwin Liu, Hiroaki Moriyama, Norio Abiru, Dongmei Miao, Liping Yu, Robert M. Taylor, Fred D. Finkelman, George S. Eisenbarth
J Clin Invest.
2002;
110(7):1021–1027
doi:10.1172/JCI15488
This article Copyright © 2002, The American Society for Clinical Investigation
Abstract
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here 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.
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