Research output: Contribution to journal › Article › peer-review
Mohammad Alhadj Ali, Yuk-Fun Liu, Sefina Arif, Danijela Tatovic, Hina Shariff, Vivienne B. Gibson, Norkhairin Yusuf, Roman Baptista, Martin Eichmann, Nedyalko Petrov, Susanne Heck, Jennie H.M. Yang, Timothy I.M. Tree, Irma Pujol-Autonell, Lorraine Yeo, Lucas R. Baumard, Rachel Stenson, Alex Howell, Alison Clark, Zoe Boult & 19 more
Original language | English |
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Article number | eaaf7779 |
Number of pages | 10 |
Journal | Science Translational Medicine |
Volume | 9 |
Issue number | 402 |
Early online date | 9 Aug 2017 |
DOIs | |
Accepted/In press | 11 Jul 2017 |
E-pub ahead of print | 9 Aug 2017 |
Published | 9 Aug 2017 |
Additional links |
Metabolic and immune effect_ALI_Acc11Jul2017_GREEN AAM
Metabolic_and_immune_effect_ALI_Acc11Jul2017_GREEN_AAM.pdf, 1.01 MB, application/pdf
Uploaded date:04 Nov 2019
Version:Accepted author manuscript
Metabolic_and_immune_effect_ALI_Acc11Jul2017_GREEN_AAM
Metabolic_and_immune_effect_ALI_Acc11Jul2017_GREEN_AAM.pdf, 722 KB, application/pdf
Uploaded date:18 Dec 2020
Version:Accepted author manuscript
Metabolic_and_immune_effect_ALI_Accepted11Jul2017_GREEN AAM
Metabolic_and_immune_effect_ALI_Acc11Jul2017_GREEN_AAM.pdf, 722 KB, application/pdf
Uploaded date:18 Dec 2020
Version:Accepted author manuscript
Accepted author manuscript
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.
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