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Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes

Lookup NU author(s): Dr Nicola Leech

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Abstract

© 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.

Publication metadata

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

Year: 2017

Volume: 9

Issue: 402

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

URL: https://doi.org/10.1126/scitranslmed.aaf7779

DOI: 10.1126/scitranslmed.aaf7779

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