Anti-peptide autoantibodies and fatal anaphylaxis in NOD mice in response to insulin self-peptides B:9-23 and B:13-23
AUTOR(ES)
Liu, Edwin
FONTE
American Society for Clinical Investigation
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=151146Documentos Relacionados
- Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23).
- Anti-peptide antibodies detect oncogene-related proteins in urine.
- Antigen mobility in the combining site of an anti-peptide antibody.
- Anti-peptide aptamers recognize amino acid sequence and bind a protein epitope.
- Human B-cell differentiation factor defined by an anti-peptide antibody and its possible role in autoantibody production.