Harmonization of Glutamic Acid Decarboxylase and Islet Antigen-2 Autoantibody Assays for National Institute of Diabetes and Digestive and Kidney Diseases Consortia

Bonifacio, Ezio; Yu, Liping; Williams, A. J. K.; Eisenbarth, George S.; Bingley, Polly J.; Marcovina, Santica M.; Adler, Kerstin; Ziegler, Anette G.; Mueller, Patricia W.; Schatz, Desmond; Krischer, Jeffrey P.; Steffes, Michael W.; Akolkar, Beena

doi:10.1210/jc.2010-0293

Cited by 260 publications

(253 citation statements)

References 16 publications

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“…Where indicated HLA typing was performed using sequence-specific primers as previously described (78). For autoantibody assays, thresholds were set as previously published (79,80) (GADA = 33 DK units/ml; IA-2A = 1.4 DK units/ml; ZnT8RA and ZnT8WA = 1.8 arbitrary units). Blood was processed no later than 3 hours after draw.…”

Section: Cd45ramentioning

confidence: 99%

Follicular helper T cell signature in type 1 diabetes

Kenefeck¹,

Wang²,

Kapadi³

et al. 2014

J. Clin. Invest.

149

161

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by negative magnetic separation (EasySep Human Naive CD4 + T cell Enrichment Kit, Stem Cell Technologies). Cells were plated at a density of 100,000 per well in a 96-well round bottom plate and stimulated with anti-CD3/28 beads (Human T-Activator Dynabeads, Life Technologies) for 5 days. Where indicated, cultures were treated with 10 ng/ml IL-12 and/or 20 ng/ml IL-2 (both from Peprotech). Statistics. Data were analyzed using Prism statistical software. Statistical significance was assessed using the Mann-Whitney test. Paired data were analyzed using a 2-tailed paired Student's t test. A P value of less than 0.05 was considered significant.

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Section: Cd45ramentioning

confidence: 99%

Follicular helper T cell signature in type 1 diabetes

Kenefeck¹,

Wang²,

Kapadi³

et al. 2014

J. Clin. Invest.

149

161

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“…[9][10][11] In the 2015 IASP Workshop, sensitivities and specificities were 52% and 100%, respectively, for mIAA, 82% and 99%, respectively, for GADA, 72% and 100%, respectively, for IA-2A, and 70% and 97%, respectively, for ZnT8A.…”

Section: Islet Autoantibody Radioassaymentioning

confidence: 99%

The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies

Sosenko

Skyler

et al. 2017

Diabetes Technology & Therapeutics

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Background: Electrochemiluminescence (ECL) assays have shown promise for enhancing the prediction of type 1 diabetes (T1D) with autoantibodies. We thus studied relatives of T1D patients to determine whether ECL assays can be used to refine risk assessments for T1D among individuals either positive for single GADA or single mIAA autoantibodies. Subjects and Methods: TrialNet Pathway to Prevention (PTP) study participants with either GADA or mIAA single autoantibodies were tested for ECL positivity during their participation in the TrialNet PTP study. Those ECL positive (ECL + ) were compared with those ECL negative (ECL -) for conversion to multiple autoantibodies, 6-month glycemic progression (PS6M), and the progression to T1D. Results: The progression to multiple autoantibodies was significantly higher for those GADA/ECL + (n = 107) than those GADA/ECL -(n = 78) (P = 0.001) and for those mIAA/ECL + (n = 24) than those mIAA/ECL -(n = 63) (P < 0.001). The hazard ratios with 95% confidence intervals were 3.42 (1.58-7.39; P < 0.01) for GADA and 8.15 (3.02-22.00; P < 0.001) for mIAA. GADA/ECL + and mIAA/ECL + participants had significantly higher PS6M values than their ECL -counterparts (P = 0.001 for GADA and P = 0.009 for mIAA). Of those GADA/ ECL + , 14% progressed to T1D; of those mIAA/ECL + , 17% progressed to T1D. Only 1 individual (positive for GADA) of the 141 who was ECL -progressed to T1D (median follow-up: 5 years). Conclusion: ECL measurements appear to have utility for natural history studies and prevention trials of individuals with single autoantibodies. Those ECL + are at appreciable risk for developing multiple autoantibodies and for glycemic progression toward T1D, whereas those ECL -are at very low risk.

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“…The Diabetes Antibody Standardization Program (DASP) 8 is a collaborative effort of the Immunology of Diabetes Society and the CDC aimed at the evaluation and improvement of assays for type 1 diabetes-associated autoantibodies, the provision of standard reference samples, and the validation of novel candidate autoantibody antigens (1,2 ). DASP supervises international workshops in which relatively large sets of coded sera from patients with type 1 diabetes and nondiabetic controls are tested for islet autoantibodies by participating centers, followed by a centralized and independent assessment of autoantibody assay performance.…”

confidence: 99%

Diabetes Antibody Standardization Program: First Proficiency Evaluation of Assays for Autoantibodies to Zinc Transporter 8

et al. 2011

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BACKGROUND Zinc transporter 8 (ZnT8) is a recently identified major autoantigen in type 1 diabetes, and autoantibodies to ZnT8 (ZnT8A) are new markers for disease prediction and diagnosis. Here we report the results of the first international proficiency evaluation of ZnT8A assays by the Diabetes Antibody Standardization Program (DASP). METHODS After a pilot workshop in 2007, an expanded ZnT8A workshop was held in 2009, with 26 participating laboratories from 13 countries submitting results of 63 different assays. ZnT8A levels were measured in coded sera from 50 patients with newly diagnosed type 1 diabetes and 100 blood donor controls. Results were analyzed comparing area under the ROC curve (ROC-AUC), sensitivity adjusted to 95% specificity (AS95), concordance of sample ZnT8A positive or negative designation, and autoantibody levels. RESULTS ZnT8A radio binding assays (RBAs) based on combined immunoprecipitation of the 2 most frequent ZnT8 COOH-terminal domain polymorphic variants showed a median ROC-AUC of 0.848 [interquartile range (IQR) 0.796–0.878] and a median AS95 of 70% (IQR 60%–72%). These RBAs were more sensitive than assays using as antigen either 1 ZnT8 variant only or chimeric constructs joining NH2- and COOH-terminal domains, assays based on immunoprecipitation and bioluminescent detection, or assays based on immunofluorescent staining of cells transfected with full-length antigen. CONCLUSIONS The DASP workshop identified immunoprecipitation-based ZnT8A assays and antigen constructs that achieved both a high degree of sensitivity and specificity and were suitable for more widespread clinical application.

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Harmonization of Glutamic Acid Decarboxylase and Islet Antigen-2 Autoantibody Assays for National Institute of Diabetes and Digestive and Kidney Diseases Consortia

Abstract: Harmonization of GADA and IA-2A is feasible using large volume working calibrators and common protocols and is an effective approach to ensure consistency in autoantibody measurements.

Cited by 260 publications

References 16 publications

Follicular helper T cell signature in type 1 diabetes

Follicular helper T cell signature in type 1 diabetes

The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies

Diabetes Antibody Standardization Program: First Proficiency Evaluation of Assays for Autoantibodies to Zinc Transporter 8

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