期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 9, 期 402, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaf7779
关键词
-
资金
- Diabetes Vaccine Development Centre
- National Health and Medical Research Council (Australia)
- Juvenile Diabetes Research Foundation
- National Institute of Health Research Biomedical Research Centre Award
- Diabetes UK Clinical Research Fellowship
- Marie Sklodowska-Curie Individual Fellowship (IF-EF)
- MRC [MR/M022927/1] Funding Source: UKRI
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 antigenDR4( 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据