Article ; Online: Progress and challenges for treating Type 1 diabetes.
2016 Volume 71, Page(s) 1–9
Abstract: It has been more than 30 years since the initial trials of Cyclosporin A to treat patients with new onset Type 1 diabetes (T1D). Since that time, there have been insights into genetic predisposition to the disease, the failures of immune tolerance, and ... ...
| Abstract | It has been more than 30 years since the initial trials of Cyclosporin A to treat patients with new onset Type 1 diabetes (T1D). Since that time, there have been insights into genetic predisposition to the disease, the failures of immune tolerance, and mechanisms that cause the immune mediated β cell destruction. The genetic loci associated affect lymphocyte development and tolerance mechanisms. Discoveries related to the roles of specific immune responses gene such as the major histocompatibility complex, PTPN22, CTLA-4, IL-2RA, as well as the mechanisms of antigen presentation in the thymus have suggested ways in which autoreactivity may follow changes in the functions of these genes that are associated with risk. Antigens that are recognized by the immune system in patients with T1D have been identified. With this information, insights into the novel cellular mechanisms leading to the initiation and orchestration of β cell killing have been developed such as the presentation of unique antigens within the islets. Clinical trials have been performed, some of which have shown efficacy in improving β cell function but none have been able to permanently prevent loss of insulin secretion. The reasons for the lack of long term success are not clear but may include the heterogeneity of the immune response and in individual responses to immune therapies, recurrence of autoimmunity after the initial effects of the therapies, or even intrinsic mechanisms of β cell death that proceeds independently of immune attack after initiation of the disease. In this review, we cover developments that have led to new therapeutics and characteristics of patients who may show the most benefits from therapies. We also identify areas of incomplete understanding that might be addressed to develop more effective therapeutic strategies. |
|---|---|
| MeSH term(s) | Animals ; Autoimmunity/immunology ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/therapy ; Disease Models, Animal ; Genetic Predisposition to Disease/genetics ; Humans ; Immune Tolerance/immunology ; Immunotherapy/methods ; Immunotherapy/trends ; Models, Genetic ; Models, Immunological |
| Language | English |
| Publishing date | 2016 |
| Publishing country | England |
| Document type | Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
| ZDB-ID | 639452-8 |
| ISSN | 1095-9157 ; 0896-8411 |
| ISSN (online) | 1095-9157 |
| ISSN | 0896-8411 |
| DOI | 10.1016/j.jaut.2016.04.004 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 2368: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.