Antigen Targets of Type 1 Diabetes Autoimmunity

Roep, Bart O.; Peakman, Mark

doi:10.1101/cshperspect.a007781

Cited by 178 publications

(158 citation statements)

References 91 publications

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“…Pre-clinical studies suggest that antigen-specific Tregs are more effective in controlling autoimmune-mediated beta cell destruction compared to polyclonal Tregs [44]. Although in T1DM target antigens have been defined [72], a major challenge lies in isolating these rarer cells from peripheral circulation, and then expanding them for clinical use. Thus, one may be best served in generating antigen-specific Tregs de novo.…”

Section: Antigen Specific Tregsmentioning

confidence: 99%

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Gitelman

Bluestone

2016

Journal of Autoimmunity

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a b s t r a c tType 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin producing beta cells. Regulatory T cells (Tregs) have been shown to be defective in this setting. Immuno-therapies targeting T cells, and resetting the balance between T effectors and Tregs, have had some initial success in preserving beta cell function. With a goal to use Tregs themselves as a novel therapeutic, we developed a technique to isolate and expand Tregs from patients with T1DM. These ex vivo expanded CD4 þ CD127 lo/À CD25 þ cells exhibit improved function and retain their T cell receptor diversity. These cells have subsequently been used in phase I clinical trials in patients with recent onset T1DM. The infusions were well tolerated, with no safety concerns. The studies are too small to assess efficacy definitively, although some individuals exhibit stable beta cell function over intervals as long as 2 years. These efforts set the stage for a larger phase II effort in new onset T1DM, and combination studies with other drugs, as well as efforts in other autoimmune diseases.

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Section: Antigen Specific Tregsmentioning

confidence: 99%

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Gitelman

Bluestone

2016

Journal of Autoimmunity

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“…New techniques such as the selective expression of beta-cell antigens using substraction microarrays have allowed for the identification of novel autoantigens recognized by CD4 + T cells despite the lack of a concurrent humoral immune responses (Neophytou et al 1996;Roep and Peakman 2012). Interestingly, some of those autoantigens (i.e.…”

Section: From Antigen Identification To Epitope Discoverymentioning

confidence: 99%

Apportioning Blame: Autoreactive CD4+ and CD8+ T Cells in Type 1 Diabetes

Varela-Calviño

Calviño-Sampedro

Gómez-Touriño

et al. 2017

Arch. Immunol. Ther. Exp.

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“…A similar process occurs spontaneously in the NOD mouse, leading to extensive beta cell loss and diabetes, though on a shorter time scale than in human T1D; this model, sharing many similar features with human T1D, has been used extensively to research the immunological processes underlying T1D (Thayer et al 2010). Many beta cell antigens, targeted by one or both of the humoral (autoantibodies) and cellular (autoreactive T cells) branches of adaptive immunity, have been identified in NOD mice and humans (Roep & Peakman 2012). Islet autoantibodies are strongly associated with T1D, with insulin, glutamic acid decarboxylase 2 (GAD2, also known as GAD65) andprotein tyrosine phosphatase, receptor type N (PTPRN, also known as IA2) autoantibodies often appearing well before diabetes onset.…”

Section: Iapp As An Autoantigen In Type 1 Diabetesmentioning

confidence: 99%

IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants

Denroche

Verchere

2018

Journal of Molecular Endocrinology

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Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2 diabetes and islet transplants, is now recognized as a contributor to beta cell dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to IAPP-derived epitopes have been described in humans, suggesting that IAPP is an islet autoantigen in type 1 diabetes. In addition, although aggregates of IAPP have not been implicated in type 1 diabetes, they are potent pro-inflammatory stimuli to innate immune cells, and thus, could influence autoimmunity. IAPP aggregates also occur rapidly in transplanted islets and likely contribute to islet transplant failure in type 1 diabetes through sterile inflammation. In addition, since type 1 diabetes is a disease of both insulin and IAPP deficiency, clinical trials have examined the potential benefits of IAPP replacement in type 1 diabetes with the injectable IAPP analogue, pramlintide. Pramlintide limits postprandial hyperglycemia by delaying gastric emptying and suppressing hyperglucagonemia, underlining the possible role of IAPP in postprandial glucose metabolism. Here, we review IAPP in the context of type 1 diabetes: from its potential involvement in type 1 diabetes pathogenesis, through its role in glucose metabolism and use of IAPP analogues as therapeutics, to its potential role in clinical islet transplant failure and considerations in this regard for future beta cell replacement strategies.

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Antigen Targets of Type 1 Diabetes Autoimmunity

Cited by 178 publications

References 91 publications

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Regulatory T cell therapy for type 1 diabetes: May the force be with you

Apportioning Blame: Autoreactive CD4+ and CD8+ T Cells in Type 1 Diabetes

IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants

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