Lookup NU author(s): Dr Nicola Leech
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© 2017 The Authors. Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen- DR4(DRB1 0401)-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months. The placebo group's daily insulin use increased by 50% over 12 months but remained unchanged in the intervention groups. C-peptide retention in treated subjects was associated with proinsulin-stimulated interleukin-10 production, increased FoxP3 expression by regulatory T cells, low baseline levels of activated b cell-specific CD8 T cells, and favorable b cell stress markers (proinsulin/C-peptide ratio). Thus, proinsulin peptide immunotherapy is safe, does not accelerate decline in b cell function, and is associated with antigen-specific and nonspecific immune modulation.
Author(s): Ali MA, Liu Y-F, Arif S, Tatovic D, Shariff H, Gibson VB, Yusuf N, Baptista R, Eichmann M, Petrov N, Heck S, Yang JHM, Tree TIM, Irma P-A, Yeo L, Baumard LR, Stenson R, Howell A, Clark A, Boult Z, Powrie J, Adams L, Wong FS, Luzio S, Dunseath G, Green K, OKeefe A, Bayly G, Thorogood N, Andrews R, Leech N, Joseph F, Nair S, Seal S, Cheung H, Beam C, Hills R, Peakman M, Dayan CM
Publication type: Article
Publication status: Published
Journal: Science Translational Medicine
Online publication date: 09/08/2017
Acceptance date: 11/07/2017
ISSN (print): 1946-6234
ISSN (electronic): 1946-6242
Publisher: American Association for the Advancement of Science
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