Bridging-type enzyme-linked immunoassay for zinc transporter 8 autoantibody measurements in adult patients with diabetes mellitus

Dunseath, Gareth; Ananieva-Jordanova, Rossitza; Coles, Rebecca; Powell, Michael J.; Amoroso, Marie; Furmaniak, Jadwiga; Smith, Bernard Rees; Dayan, Colin; Luzio, Stephen Denis

doi:10.1016/j.cca.2015.05.010

Cited by 17 publications

(10 citation statements)

References 32 publications

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“…Seeing as the incidence of type 1 diabetes in white people is much higher than in Japanese people, the frequency of incidental recruitment of anti‐islet autoantibody‐positive healthy individuals might also be higher in the white population. With this newly determined cut‐off value, the prevalence of ZnT8A in the 324 patients with type 1 diabetes was 24.7%, which was lower than in previous reports 6,14,15 . As the higher prevalence of ZnT8A in acute‐onset type 1 diabetic patients in comparison with the slowly progressive form observed in the present study was in accordance with previous reports, the possible reason for this discrepancy could be due to the differences in age, the duration of diabetes or the proportion of the subtype of type 1 diabetes 16 .…”

Section: Discussionsupporting

confidence: 78%

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma‐associated antigen‐2 autoantibodies in the identification and characterization of Japanese type 1 diabetes

Kawasaki

Oikawa

Okada³

et al. 2020

J of Diabetes Invest

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Aims/Introduction This study aimed to investigate the significance of zinc transporter 8 autoantibody (ZnT8A) in identifying and characterizing autoimmune‐mediated type 1 diabetes in Japanese individuals. Methods ZnT8A were determined in 324 patients with type 1 diabetes, 191 phenotypic type 2 diabetes and 288 healthy control individuals using bridging‐type enzyme‐linked immunosorbent assay in addition to autoantibodies to glutamic acid decarboxylase and insulinoma‐associated antigen‐2. Results We set a cut‐off value of 10.0 U/mL, and 25% of the type 1 diabetic patients had ZnT8A levels exceeding this level. The prevalence of ZnT8A was significantly higher in patients with acute‐onset type 1 diabetes than in those with slowly progressive and fulminant type 1 diabetes (P < 0.05). ZnT8A were more frequent in patients aged ≤10 years, but less frequent in patients with duration ≥5 years (P < 0.05). ZnT8A were detected in 5.2% of phenotypic type 2 diabetic patients, with 90% of these being ZnT8A‐single‐positive. Furthermore, the ZnT8A levels in the phenotypic type 2 diabetes cohort (143.8 ± 194.9 U/mL) were significantly higher than those in the type 1 diabetes cohort (22.9 ± 8.3 U/mL, P < 0.05). In the acute‐onset and slowly progressive type 1 diabetic patients with duration ≤5 years, additional measurement of glutamic acid decarboxylase autoantibodies significantly increased the disease sensitivity in patients aged ≤10 years, but not in patients aged ≥11 years (11.7 vs 3.6%, P < 0.05). Multivariate analysis showed that ZnT8A positivity was independently associated with age at sampling and insulinoma‐associated antigen‐2 autoantibody positivity. Conclusions These results suggest that the bridging‐type ZnT8A enzyme‐linked immunosorbent assay might provide a valuable additional marker for Japanese patients with type 1 diabetes, which could, in turn, allow for an increase in the number of identifiable cases and differentiate clinical phenotypes.

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Section: Discussionsupporting

confidence: 78%

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma‐associated antigen‐2 autoantibodies in the identification and characterization of Japanese type 1 diabetes

Kawasaki

Oikawa

Okada³

et al. 2020

J of Diabetes Invest

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“…The Diabetes Antibody Standardization Program workshop identified that ZnT8A measured by radioligand assay showed a median ROC-AUC of 0.848. 24) Dunseath et al 25) showed an AUC of 0.80, 54% sensitivity, and 99% specificity by conducting ROC analysis of ZnT8A by ELISA in type 1 diabetics and healthy blood donors. In this study, the ROC-AUC for ZnT8A by ELISA is 0.71, 73.3% sensitivity, and 72.2% specificity.…”

Section: Discussionmentioning

confidence: 99%

Zinc transporter 8 autoantibody in the diagnosis of type 1 diabetes in children

2020

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Background: Type 1 diabetes (T1D) is an organ-specific autoimmune disease related to the autoimmune response against pancreatic β-cells. Zinc transporter 8 (ZnT8), an islet-specific gene product localized to the β-cell insulin granule, was recently identified as an autoantigen in T1D.Purpose: To evaluate the use of ZnT8 autoantibody (ZnT8A) for diagnosing T1D.Methods: This case-control study was conducted at Dr. Soetomo General Hospital, Surabaya, Indonesia, from March to May 2019. Children younger than 18 years of age with T1D based on the International Society for Pediatric and Adolescent Diabetes guideline and healthy controls were included. We measured ZnT8A level using enzyme-linked immunosorbent assay (cutoff value, 0.315).Results: There were 30 children with T1D (50.0% boys; mean age, 11.3±3.7 years) and 18 healthy controls (44.4% boys; mean age, 8.3±3.1 years); 1 patient in each group was Madurese, while the others were Javanese. Twenty-two of 30 subjects with T1D (73.3%) tested positive for ZnT8A compared to 5 of 18 controls (27.8%) (<i>P</i>=0.02; odds ratio, 7.15; 95% confidence interval, 1.93–26.52). When ZnT8A-positive and -negative T1D cases were compared, no differences were detected in age at diagnosis, duration of diabetes, presence of ketoacidosis, body mass index, glycosylated hemoglobin concentration, or C-peptide concentrations.Conclusion: ZnT8A may be useful in the diagnosis of T1D.

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“…LIPS has a similar assay format to gold standard RIAs and provides an alternative to radioisotope use. ( d ) The routinely used commercial ZnT8 bridge ELISA (developed by RSR) employs plates coated in C-terminal ZnT8 and detects ZnT8A by means of a biotin–streptavidin–peroxidase system, where the peroxidase acts as a substrate to 3,3′, 5,5′-tetramethylbenzidine (TMB) to create a colourogenic reaction proportionate to the level of ZnT8A [66]. ( e ) A method for measuring ZnT8A responses outside of the C-terminal, through a three-dimensional format, has been proposed, creating scope for elucidating conformational epitopes.…”

Section: What Benefits Could New Assays For Znt8a Offer For Prediction?mentioning

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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Bridging-type enzyme-linked immunoassay for zinc transporter 8 autoantibody measurements in adult patients with diabetes mellitus

Cited by 17 publications

References 32 publications

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma‐associated antigen‐2 autoantibodies in the identification and characterization of Japanese type 1 diabetes

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma‐associated antigen‐2 autoantibodies in the identification and characterization of Japanese type 1 diabetes

Zinc transporter 8 autoantibody in the diagnosis of type 1 diabetes in children

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

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