Mohammad Alhadj Ali1,*, Yuk-Fun Liu2,3,*, Sefina Arif2, Danijela Tatovic1, Hina Shariff2, Vivienne B. Gibson2, Norkhairin Yusuf2, Roman Baptista2,4, Martin Eichmann2, Nedyalko Petrov4, Susanne Heck4, Jennie H. M. Yang2, Timothy I. M. Tree2, Irma Pujol-Autonell2, Lorraine Yeo2, Lucas R. Baumard2, Rachel Stenson1, Alex Howell1, Alison Clark1, Zoe Boult5, Jake Powrie3, Laura Adams3, Florence S. Wong1, Stephen Luzio6, Gareth Dunseath6, Kate Green7, Alison O’Keefe7, Graham Bayly7, Natasha Thorogood7, Robert Andrews7, Nicola Leech8, Frank Joseph9, Sunil Nair9, Susan Seal9, HoYee Cheung9, Craig Beam10, Robert Hills11, Mark Peakman2,4,12,†,‡ and Colin M. Dayan1,‡
Abstract
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 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.
this is great, thanks for sharing
very nicely describe all points in a short manner