Biomedical subjects

Edwin Liu

Publications and source records attributed to Edwin Liu.

20 records · Page 2Linked to original sources

PubMed2002

Induction of insulin autoantibodies and protection from diabetes with subcutaneous insulin B:9-23 peptide without adjuvant.

Insulin B chain peptide B:9-23 given with incomplete Freund's adjuvant (IFA) subcutaneously to NOD and BALB/c mice induces insulin autoantibodies (IAA). We also found that subcutaneous administration of the peptide without adjuvant induced IAA in normal BALB/c mice. The autoantibodies react with intact insulin and cannot be absorbed by the B:9-23 peptide. With the induction of IAA by the self-peptide without adjuvant, we hypothesized that the peptide given subcutaneously without adjuvant would prevent the development of diabetes mellitus in NOD mice. The peptide B:9-23, when given in standard doses of 100 microg and low doses of 10 microg, protected female NOD mice versus unvaccinated controls from diabetes. Presently, NOD mice vaccinated with the standard dose and the low dose have a 44% and 60% survival, respectively, at 26 weeks compared to controls with a 10% diabetes-free survival at 22 weeks (n = 10 for each group, P < 0.001 for both vaccine doses). As expected, the level of IAA expressed was significantly higher for the vaccinated mice versus the control group. We conclude that insulin B chain peptide B:9-23 can confer protection from diabetes in NOD mice even when administered subcutaneously without adjuvant.

Adjuvants, Immunologic↗

PubMed2002

Anti-peptide autoantibodies and fatal anaphylaxis in NOD mice in response to insulin self-peptides B:9-23 and B:13-23.

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.

Anaphylaxis↗