Reference Database

Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes.
Alhadj Ali, Mohammad
Liu, Yuk-Fun
Arif, Sefina
Tatovic, Danijela
Shariff, Hina
Gibson, Vivienne B
Yusuf, Norkhairin
Baptista, Roman
Eichmann, Martin
Petrov, Nedyalko
Heck, Susanne
Yang, Jennie H M
Tree, Timothy I M
Pujol-Autonell, Irma
Yeo, Lorraine
Baumard, Lucas R
Stenson, Rachel
Howell, Alex
Clark, Alison
Boult, Zoe
Powrie, Jake
Adams, Laura
Wong, Florence S
Luzio, Stephen
Dunseath, Gareth
Green, Kate
O'Keefe, Alison
Bayly, Graham
Thorogood, Natasha
Andrews, Robert
Leech, Nicola
Joseph, Frank
Nair, Sunil
Seal, Susan
Cheung, HoYee
Beam, Craig
Hills, Robert
Peakman, Mark
Dayan, Colin M
Science translational medicine 2017 Aug 09;9:

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()-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 12 months 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 β cell-specific CD8 T cells, and favorable β cell stress markers (proinsulin/C-peptide ratio). Thus, proinsulin peptide immunotherapy is safe, does not accelerate decline in β cell function, and is associated with antigen-specific and nonspecific immune modulation.

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