Glutamic acid decarboxylase and IA-2 autoantibodies in type 1 diabetes: comparing sample substrates for autoantibody determinations

Wasserfall, Clive; Atkinson, M. A.; Jodoin, Eric; Schatz, Desmond; She, Jin‐Xiong; Henderson, L. Omar; Ellis, T. M.

doi:10.1034/j.1399-5448.2000.010103.x

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…Subjects and serum samples: Study subjects were participants in the PANDA study (prospective assessment in newborns for diabetes autoimmunity) in the Southeast US [18]. All study subjects were genotyped for HLA-DQB1 and evaluated for three autoantibodies (IA-2A, GADA, and IAA) using established methods [2,19]. Subjects with high-risk genes are monitored for the appearance of islet autoantibodies and clinical diabetes at regular intervals.…”

Section: Blood Collection and Storagementioning

confidence: 99%

Assessing the utility of SELDI-TOF and model averaging for serum proteomic biomarker discovery

et al. 2006

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The SELDI-TOF technique was used to profile serum proteins from Type 1 diabetes (T1D) patients and healthy autoantibody-negative (AbN) controls. Univariate and multivariate analyses were performed to identify putative biomarkers for T1D and to assess the reproducibility of the SELDI technique. We found 146 protein/peptide peaks (581 total peaks discovered) in human serum showing statistical differences in expression levels between T1D patients and controls, with 84% of these peaks showing technical replication. Because individual proteins did not offer great power for disease prediction, we used our model averaging approach that combines the information from multiple multivariate models to accurately classify T1D and control subjects (88.9% specificity and 90.0% sensitivity). Analyses of a test subset of the data showed less accuracy (82.8% specificity and 76.2% sensitivity), although the results are still positive. Unfortunately, no multivariate model could be replicated using the same samples. This first attempt of high throughput analyses of the human serum proteome in T1D patients suggests that model averaging is a viable method for developing biomarkers; however, the reproducibility of SELDI-TOF is currently not sufficient to be used for classification of complex diseases like T1D.

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Section: Blood Collection and Storagementioning

confidence: 99%

Assessing the utility of SELDI-TOF and model averaging for serum proteomic biomarker discovery

et al. 2006

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“…Furthermore, there is limited experience of using these assays with capillary blood. [15][16][17] To overcome this problem, we have collaborated with RSR Ltd., Cardiff, UK, to develop a screening assay for one-shot detection of autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD65), insulinoma-associated antigen 2 (IA-2) and zinc transporter 8 (ZnT8) using a sample volume suitable for capillary blood collection. This assay allows us to identify children positive for at least one of these autoantibodies; these children can then be followed through further screening for autoantibodies to GAD65, IA-2, ZnT8 and insulin for the diagnosis of pre-type 1 diabetes.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study

et al. 2016

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IntroductionType 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care.Methods and analysisChildren aged 2–5 years in Bavaria, Germany, will be tested for the presence of multiple islet autoantibodies. Between February 2015 and December 2016, 100 000 children will be screened by primary care paediatricians. Islet autoantibodies are measured in capillary blood samples using a multiplex three-screen ELISA. Samples with ELISA results >97.5th centile are retested using reference radiobinding assays. A venous blood sample is also obtained to confirm the autoantibody status of children with at least two autoantibodies. Children with confirmed multiple islet autoantibodies are diagnosed with pre-type 1 diabetes. These children and their parents are invited to participate in an education and counselling programme at a local diabetes centre. Depression and anxiety, and burden of early diagnosis are also assessed.ResultsOf the 1027 Bavarian paediatricians, 39.3% are participating in the study. Overall, 26 760 children have been screened between February 2015 and November 2015. Capillary blood collection was sufficient in volume for islet autoantibody detection in 99.46% of the children. The remaining 0.54% had insufficient blood volume collected. Of the 26 760 capillary samples tested, 0.39% were positive for at least two islet autoantibodies.DiscussionStaging for early type 1 diabetes within a public health setting appears to be feasible. The study may set new standards for the early diagnosis of type 1 diabetes and education.Ethics disseminationThe study was approved by the ethics committee of Technische Universität München (Nr. 70/14).

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“…In DASP 2005, our in-house RIA-GADA assay gave a sensitivity of 76% and a specificity of 91% for serum samples, and our in-house RIA-IA-2A assay gave a sensitivity of 72% and a specificity of 100%. GADA and IA-2A have been analysed in whole blood eluates with RIA assays with high performance [18, 19]. …”

Section: Introductionmentioning

confidence: 99%

Comparison of Measurements of Autoantibodies to Glutamic Acid Decarboxylase and Islet Antigen-2 in Whole Blood Eluates from Dried Blood Spots Using the RSR-Enzyme Linked Immunosorbent Assay Kits and In-House Radioimmunoassays

Persson

Becker

Hansson

et al. 2010

Experimental Diabetes Research

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To evaluate the performance of dried blood spots (DBSs) with subsequent analyses of glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A) with the RSR-ELISAs, we selected 80 children newly diagnosed with type 1 diabetes and 120 healthy women. DBSs from patients and controls were used for RSR-ELISAs while patients samples were analysed also with in-house RIAs. The RSR-ELISA-GADA performed well with a specificity of 100%, albeit sensitivity (46%) was lower compared to in RIA (56%; P = .008). No prozone effect was observed after dilution of discrepant samples. RSR-ELISA-IA-2A achieved specificity of 69% and sensitivity was lower (59%) compared with RIA (66%; P < .001). Negative or low positive patients and control samples in the RSR-ELISA-IA-2A increased after dilution. Eluates from DBS can readily be used to analyse GADA with the RSR-ELISA, even if low levels of autoantibodies were not detected. Some factor could disturb RSR-ELISA-IA-2A analyses.

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Glutamic acid decarboxylase and IA-2 autoantibodies in type 1 diabetes: comparing sample substrates for autoantibody determinations

Cited by 10 publications

References 13 publications

Assessing the utility of SELDI-TOF and model averaging for serum proteomic biomarker discovery

Assessing the utility of SELDI-TOF and model averaging for serum proteomic biomarker discovery

Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study

Comparison of Measurements of Autoantibodies to Glutamic Acid Decarboxylase and Islet Antigen-2 in Whole Blood Eluates from Dried Blood Spots Using the RSR-Enzyme Linked Immunosorbent Assay Kits and In-House Radioimmunoassays

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