Clinical and Experimental Treatment of Type 1 Diabetes

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2022 Aug 18

PMID 35980300

Authors

S Alice Long

Jane H Buckner

Affiliations

Soon will be listed here.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease resulting in the destruction of the insulin-producing pancreatic beta cells. Disease progression occurs along a trajectory from genetic risk, the development of islet autoantibodies, and autoreactive T cells ultimately progressing to clinical disease. Natural history studies and mechanistic studies linked to clinical trials have provided insight into the role of the immune system in disease pathogenesis. Here, we review our current understanding of the underlying etiology of T1D, focusing on the immune cell types that have been implicated in progression from pre-symptomatic T1D to clinical diagnosis and established disease. This knowledge has been foundational for the development of immunotherapies aimed at the prevention and treatment of T1D.

Citing Articles

Antigen-specific immunotherapies for autoimmune disease.

Buckner J Nat Rev Rheumatol. 2024; 21(2):88-97.

PMID: 39681709 DOI: 10.1038/s41584-024-01201-w.

Clinical and Experimental Immunology: highlights from 2022.

Taams L, Taylor R Clin Exp Immunol. 2023; 212(1):11-13.

PMID: 36805630 PMC: 10081112. DOI: 10.1093/cei/uxad018.

Introducing our new series: Clinical and Experimental Treatment of….

Zaiss D Clin Exp Immunol. 2022; 210(2):104.

PMID: 36355570 PMC: 9750822. DOI: 10.1093/cei/uxac100.

References

Ferreira R, Simons H, Thompson W, Cutler A, Dopico X, Smyth D . IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients. Diabetologia. 2015; 58(4):781-90. PMC: 4351433. DOI: 10.1007/s00125-015-3509-8. View

Orban T, Bundy B, Becker D, DiMeglio L, Gitelman S, Goland R . Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. Diabetes Care. 2013; 37(4):1069-75. PMC: 3964491. DOI: 10.2337/dc13-0604. View

Dabelea D, Mayer-Davis E, Saydah S, Imperatore G, Linder B, Divers J . Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA. 2014; 311(17):1778-86. PMC: 4368900. DOI: 10.1001/jama.2014.3201. View

Cerosaletti K, Barahmand-Pour-Whitman F, Yang J, DeBerg H, Dufort M, Murray S . Single-Cell RNA Sequencing Reveals Expanded Clones of Islet Antigen-Reactive CD4 T Cells in Peripheral Blood of Subjects with Type 1 Diabetes. J Immunol. 2017; 199(1):323-335. PMC: 5499675. DOI: 10.4049/jimmunol.1700172. View

Robertson C, Inshaw J, Onengut-Gumuscu S, Chen W, Santa Cruz D, Yang H . Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes. Nat Genet. 2021; 53(7):962-971. PMC: 8273124. DOI: 10.1038/s41588-021-00880-5. View

Krischer J, Lynch K, Schatz D, Ilonen J, Lernmark A, Hagopian W . The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia. 2015; 58(5):980-7. PMC: 4393776. DOI: 10.1007/s00125-015-3514-y. View

Mishra A, Hawkins R . Three-dimensional genome architecture and emerging technologies: looping in disease. Genome Med. 2017; 9(1):87. PMC: 5623062. DOI: 10.1186/s13073-017-0477-2. View

Herold K, Bundy B, Long S, Bluestone J, DiMeglio L, Dufort M . An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019; 381(7):603-613. PMC: 6776880. DOI: 10.1056/NEJMoa1902226. View

Ekman I, Ihantola E, Viisanen T, Rao D, Nanto-Salonen K, Knip M . Circulating CXCR5PD-1 peripheral T helper cells are associated with progression to type 1 diabetes. Diabetologia. 2019; 62(9):1681-1688. PMC: 6677711. DOI: 10.1007/s00125-019-4936-8. View

10.

Ziegler A, Rewers M, Simell O, Simell T, Lempainen J, Steck A . Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013; 309(23):2473-9. PMC: 4878912. DOI: 10.1001/jama.2013.6285. View

11.

Viisanen T, Ihantola E, Nanto-Salonen K, Hyoty H, Nurminen N, Selvenius J . Circulating CXCR5+PD-1+ICOS+ Follicular T Helper Cells Are Increased Close to the Diagnosis of Type 1 Diabetes in Children With Multiple Autoantibodies. Diabetes. 2017; 66(2):437-447. DOI: 10.2337/db16-0714. View

12.

Steck A, Vehik K, Bonifacio E, Lernmark A, Ziegler A, Hagopian W . Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care. 2015; 38(5):808-13. PMC: 4407751. DOI: 10.2337/dc14-2426. View

13.

Hagopian W, Ferry Jr R, Sherry N, Carlin D, Bonvini E, Johnson S . Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial. Diabetes. 2013; 62(11):3901-8. PMC: 3806608. DOI: 10.2337/db13-0236. View

14.

von Herrath M, Bain S, Bode B, Clausen J, Coppieters K, Gaysina L . Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2021; 9(4):212-224. DOI: 10.1016/S2213-8587(21)00019-X. View

15.

Xhonneux L, Knight O, Lernmark A, Bonifacio E, Hagopian W, Rewers M . Transcriptional networks in at-risk individuals identify signatures of type 1 diabetes progression. Sci Transl Med. 2021; 13(587). PMC: 8447843. DOI: 10.1126/scitranslmed.abd5666. View

16.

Schwedhelm K, Thorpe J, Murray S, Gavin M, Speake C, Greenbaum C . Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state. Clin Immunol. 2017; 181:67-74. PMC: 5564451. DOI: 10.1016/j.clim.2017.06.004. View

17.

Barrett J, Clayton D, Concannon P, Akolkar B, Cooper J, Erlich H . Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet. 2009; 41(6):703-7. PMC: 2889014. DOI: 10.1038/ng.381. View

18.

de Klerk E, Hebrok M . Stem Cell-Based Clinical Trials for Diabetes Mellitus. Front Endocrinol (Lausanne). 2021; 12:631463. PMC: 7953062. DOI: 10.3389/fendo.2021.631463. View

19.

Haller M, Long S, Blanchfield J, Schatz D, Skyler J, Krischer J . Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data. Diabetes. 2019; 68(6):1267-1276. PMC: 6610026. DOI: 10.2337/db19-0057. View

20.

Habib T, Funk A, Rieck M, Brahmandam A, Dai X, Panigrahi A . Altered B cell homeostasis is associated with type I diabetes and carriers of the PTPN22 allelic variant. J Immunol. 2011; 188(1):487-96. PMC: 3670766. DOI: 10.4049/jimmunol.1102176. View