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| Article Authors: | D G Alleva; R A Maki; A L Putnam; J M Robinson; M S Kipnes; P Dandona; J B Marks; D L Simmons; C J Greenbaum; R G Jimenez; P J Conlon; P A Gottlieb |
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| Article Title: | Immunomodulation in type 1 diabetes by NBI-6024, an altered peptide ligand of the insulin B epitope. |
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| Reference ID: | 1007462 |
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| Abstract: | NBI-6024 is an altered peptide ligand (APL) corresponding to the 9-23 amino acid region of the insulin B chain (B(9-23)), an epitope recognized by inflammatory interferon-gamma-producing T helper (Th)1 lymphocytes in type 1 diabetic patients. Immunomodulatory effects of NBI-6024 administration in recent-onset diabetic patients in a phase I clinical trial (NBI-6024-0003) were measured in peripheral blood mononuclear cells using the enzyme-linked immunosorbent spot assay. Analysis of the mean magnitude of cytokine responses to B(9-23) and NBI-6024 for each cohort showed significant increases in interleukin-5 responses (a Th2 regulatory phenotype) in cohorts that received APL relative to those receiving placebo. A responder analysis showed that Th1 responses to B(9-23) and NBI-6024 were observed almost exclusively in the placebo-treated diabetic population but not in nondiabetic control subjects and that APL administration (five biweekly subcutaneous injections) significantly and dose-dependently reduced the percentage of patients with these Th1 responses. The results of this phase I clinical study strongly suggest that NBI-6024 treatment shifted the Th1 pathogenic responses in recent-onset type 1 diabetic patients to a protective Th2 regulatory phenotype. The significance of these findings on the clinical outcome of disease is currently under investigation in a phase II multidose study. |
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| Affiliations: | Neurocrine Biosciences, Inc., San Diego, CA 92130, USA. |
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| Date: | 2006 |
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| Reference Type: | Literature |
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| PubMed ID: | 16398702 |
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| Journal: | Scand J Immunol |
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| Journal Volume: | 63 |
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| Article Pages: | 59-69 |
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| Journal ISSN: | 1365-3083 |
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| Article Chemical List: | Cytokines;Immunodominant Epitopes;Immunologic Factors;NBI6024;Peptide Fragments;insulin B (9-23);Insulin;Interferon-gamma |
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| Article MeSH List: | Adolescent; Adult; Child; Cytokines(metabolism); Diabetes Mellitus, Type 1(immunology); Female; Humans; Immunodominant Epitopes(administration & dosage); Immunologic Factors(administration & dosage); Insulin(administration & dosage); Interferon-gamma(metabolism); Male; Peptide Fragments(administration & dosage); Th1 Cells(immunology); Th2 Cells(immunology) |
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| Curation Last Updated: | 2013-05-28 21:11:33 |
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