High frequency of autoantibodies in patients with long duration type 1 diabetes

Richardson, Carolyn C.; Dromey, James A.; McLaughlin, Kerry A.; Morgan, Diana; Bodansky, H. J.; Feltbower, Richard; Barnett, Anthony; Gill, Geoffrey; Bain, Steve; Christie, Michael R.

doi:10.1007/s00125-013-3017-7

Cited by 21 publications

(15 citation statements)

References 10 publications

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“…Even after >14 years of diabetes duration, 34% of the patients were positive for GADA, and carriers of the LPP risk variant had a 36% increased probability for GADA positivity. This frequency of GADA positivity is comparable to other cohorts of patients with long-standing diabetes ( 31 , 32 ). Although type 1 diabetes is thought to result from an irreversible destruction of β-cells, some long-standing patients have detectable functioning β-cells ( 33 – 35 ), indicating either surviving β-cells or continued renewal due to ongoing autoimmune destruction.…”

Section: Discussionsupporting

confidence: 85%

Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

et al. 2015

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Islet autoantibodies detected at disease onset in patients with type 1 diabetes are signs of an autoimmune destruction of the insulin-producing β-cells. To further investigate the genetic determinants of autoantibody positivity, we performed dense immune-focused genotyping on the Immunochip array and tested for association with seven disease-specific autoantibodies in a large cross-sectional cohort of 6,160 type 1 diabetes–affected siblings. The genetic association with positivity for GAD autoantibodies (GADAs), IA2 antigen (IA-2A), zinc transporter 8, thyroid peroxidase, gastric parietal cells (PCAs), tissue transglutaminase, and 21-hydroxylase was tested using a linear mixed-model regression approach to simultaneously control for population structure and family relatedness. Four loci were associated with autoantibody positivity at genome-wide significance. Positivity for GADA was associated with 3q28/LPP, for IA-2A with 1q23/FCRL3 and 11q13/RELA, and for PCAs with 2q24/IFIH1. The 3q28 locus showed association after only 3 years duration and might therefore be a marker of persistent GADA positivity. The 1q23, 11q13, and 2q24 loci were associated with autoantibodies close to diabetes onset and constitute candidates for early screening. Major susceptibility loci for islet autoantibodies are separate from type 1 diabetes risk, which may have consequences for intervention strategies to reduce autoimmunity.

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Section: Discussionsupporting

confidence: 85%

Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

et al. 2015

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“…However, another study in individuals with younger onset showed that high positivity for ZnT8A at diagnosis was associated with lower C-peptide levels and increased insulin dose within the first 2 years after diagnosis, despite similar levels at disease onset [56]. In a minority of individuals where ZnT8A persist for decades after diagnosis, cross-sectional studies have also failed to reach a consensus about the relationship between ZnT8A and C-peptide [57–59]. These contrasting findings could be explained if age at diagnosis influences this association.…”

Section: Znt8a As a Biomarker Of Insulin Secretory Capacity Post Diagmentioning

confidence: 99%

What has zinc transporter 8 autoimmunity taught us about type 1 diabetes?

Williams

Long

2019

Diabetologia

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Zinc transporter 8 (ZnT8), a protein highly specific to pancreatic insulin-producing beta cells, is vital for the biosynthesis and secretion of insulin. ZnT8 autoantibodies (ZnT8A) are among the most recently discovered and least-characterised islet autoantibodies. In combination with autoantibodies to several other islet antigens, including insulin, ZnT8A help predict risk of future type 1 diabetes. Often, ZnT8A appear later in the pathogenic process leading to type 1 diabetes, suggesting that the antigen is recognised as part of the spreading, rather than the initial, autoimmune response. The development of autoantibodies to different forms of ZnT8 depends on the genotype of an individual for a polymorphic ZnT8 residue. This genetic variant is associated with susceptibility to type 2 but not type 1 diabetes. Levels of ZnT8A often fall rapidly after diagnosis while other islet autoantibodies can persist for many years. In this review, we consider the contribution made by ZnT8 to our understanding of type 1 diabetes over the past decade and what remains to be investigated in future research.Electronic supplementary materialThe online version of this article (10.1007/s00125-019-04975-x) contains a slideset of the figures for download, which is available to authorised users.

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“…[ 47 ] Nevertheless, ZnT8A could be detected within 25 years after T1DM onset (6.7%), and even in patients with T1DM for more than 50 years. [ 47 49 ]…”

Section: Linical a Pplications Of mentioning

confidence: 99%

Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus

Huang

Zhou

2015

Chinese Medical Journal

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Objective:To evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM.Data Sources:A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: “ZnT8,” “type 1 diabetes,” “latent autoimmune diabetes in adults,” “type 2 diabetes,” “islet autoantibodies,” “zinc supplement,” “T cells,” “β cell,” “immune therapy.” We also searched the reference lists of selected articles.Study Selection:English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed.Results:The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy.Conclusions:ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.

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High frequency of autoantibodies in patients with long duration type 1 diabetes

Abstract: No abstract [Research letter

Cited by 21 publications

References 10 publications

Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

What has zinc transporter 8 autoimmunity taught us about type 1 diabetes?

Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus

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