Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes.
Sci Transl Med
; 9(402)2017 08 09.
Article
em En
| MEDLINE
| ID: mdl-28794283
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 ß cell-specific CD8 T cells, and favorable ß cell stress markers (proinsulin/C-peptide ratio). Thus, proinsulin peptide immunotherapy is safe, does not accelerate decline in ß cell function, and is associated with antigen-specific and nonspecific immune modulation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Proinsulina
/
Diabetes Mellitus Tipo 1
/
Imunoterapia
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Sci Transl Med
Ano de publicação:
2017
Tipo de documento:
Article