GAD autoantibody affinity in schoolchildren from the general population

Bender, Christine; Schlosser, Michael; Christen, Urs; Ziegler, Anette G.; Achenbach, Peter

doi:10.1007/s00125-014-3294-9

Cited by 26 publications

(20 citation statements)

References 35 publications

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“…All discordant samples, except one, used in the present study were obtained from long‐standing patients with type 1 diabetes. As it has been reported that GADA affinity remained relatively constant for >10 years in GADA‐positive non‐diabetic schoolchildren, the duration of type 1 diabetes might not affect GADA affinity. However, it needs to be confirmed whether GADA affinity remains constant after the onset of type 1 diabetes using follow‐up samples.One limitation of the current study was that it was a cross‐sectional study with a relatively small sample size, and did not have data on insulin secretory capacity.…”

Section: Discussionmentioning

confidence: 85%

Discrepancy of glutamic acid decarboxylase 65 autoantibody results between RSR radioimmunoassay and enzyme‐linked immunosorbent assay in patients with type 1 diabetes is related to autoantibody affinity

Kawasaki

Okada²,

Uchida

et al. 2019

J of Diabetes Invest

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Aim/Introduction Autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) are a valuable diagnostic and predictive marker for type 1 diabetes. Recently, it has been reported that a significant proportion of sera in the commercial RSR radioimmunoassay (RIA) that have tested positive for GADA have then turned negative in RSR enzyme‐linked immunosorbent assay (ELISA) tests in patients with type 1 diabetes. The present study aimed to investigate whether the GADA result discrepancies between RSR‐RIA and RSR‐ELISA are related to autoantibody affinity. Methods GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 in 12 discordant samples (5 RIA[+]/ELISA[−] and 7 RIA[−]/ELISA[+] sera). Furthermore, the effect of the initial incubation time on the GADA positivity was also examined using the ELISA test. Results GADA affinities were >10 10 L/mol in two of five RIA(+)/ELISA(−) and all of seven RIA(−)/ELISA(+) sera. After an initial incubation time longer than the recommended 1 h, the GADA titer in three of five RIA(+)/ELISA(−) sera and all RIA(−)/ELISA(+) sera increased 1.6‐ to 100‐fold. However, the titer in 12 GADA‐negative sera from healthy controls remained unchanged after the longer incubation. The increment ratio of GADA titer was positively correlated with GADA affinity ( r = 0.991, P < 0.001). Conclusions The RSR‐RIA test identifies both high‐ and low‐affinity GADA, whereas the RSR‐ELISA test identifies only high‐affinity GADA. A longer initial incubation time in the RSR‐ELISA test increases the sensitivity of GADA with the same specificity in patients with type 1 diabetes.

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Section: Discussionmentioning

confidence: 85%

Discrepancy of glutamic acid decarboxylase 65 autoantibody results between RSR radioimmunoassay and enzyme‐linked immunosorbent assay in patients with type 1 diabetes is related to autoantibody affinity

Kawasaki

Okada²,

Uchida

et al. 2019

J of Diabetes Invest

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show abstract

“…In fact, it is believed that the bridging conformation favors the recognition of high-affinity antibodies, contributing to the good specificity [14]. Given that researches say that the existence of high-affinity GADA is more closely associated with the progression of type 1 DM [15,16], the possible high disease activity in GADA-ELISA-positive and GADA-RIA-positive SPIDDM is easily understandable.…”

Section: Discussionmentioning

confidence: 99%

Slowly progressive insulin-dependent (type 1) diabetes positive for anti-GAD antibody ELISA test may be strongly associated with a future insulin-dependent state

et al. 2017

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“…Our addition of an N-terminal methionine to GADA (96-585) to allow protein expression is unlikely to have affected antibody binding as it is neither highly charged nor bulky. The inclusion of affinity measurements may also help to identify GADA-positive individuals who are at increased risk of diabetes progression (12,17). The potential for truncated GAD 65 labels to identify patients with slowonset autoimmune diabetes in adults with a clinical presentation of type 2 diabetes also needs to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Reactivity to N-Terminally Truncated GAD65(96–585) Identifies GAD Autoantibodies That Are More Closely Associated With Diabetes Progression in Relatives of Patients With Type 1 Diabetes

Williams

Lampasona²,

Wyatt

et al. 2015

Diabetes

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GAD autoantibodies (GADAs) identify individuals at increased risk of developing type 1 diabetes, but many people currently found to be GADA positive are unlikely to progress to clinical disease. More specific GADA assays are therefore needed. Recent international workshops have shown that the reactivity of sera from healthy donors varies according to assay type and indicated that the use of N-terminally truncated GAD 65 radiolabels in GADA radiobinding assays is associated with higher specificity. To determine whether a radiobinding assay using radiolabeled GAD 65 (96-585) identified individuals who are at higher risk of developing diabetes, samples from recent-onset patients and GADA-positive first-degree relatives participating in the Bart's-Oxford type 1 diabetes family study were reassayed with full-length or N-terminally truncated GAD using the National Institute of Diabetes and Digestive and Kidney Diseases harmonized protocol. The sensitivity in patients was the same with both labels, but fewer relatives retested positive with truncated GAD. Among relatives who progressed to diabetes, similar proportions were found to be GADA positive when tested with either label, but because of their higher specificity the cumulative risk of diabetes was higher in those with autoantibodies to GAD 65 (96-585). Autoantibodies to GAD 65 (96-585) in relatives are more closely associated with diabetes risk than those to fulllength GAD, suggesting that assays using N-terminally truncated GAD should be used to select participants for intervention trials.

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GAD autoantibody affinity in schoolchildren from the general population

Cited by 26 publications

References 35 publications

Discrepancy of glutamic acid decarboxylase 65 autoantibody results between RSR radioimmunoassay and enzyme‐linked immunosorbent assay in patients with type 1 diabetes is related to autoantibody affinity

Discrepancy of glutamic acid decarboxylase 65 autoantibody results between RSR radioimmunoassay and enzyme‐linked immunosorbent assay in patients with type 1 diabetes is related to autoantibody affinity

Slowly progressive insulin-dependent (type 1) diabetes positive for anti-GAD antibody ELISA test may be strongly associated with a future insulin-dependent state

Reactivity to N-Terminally Truncated GAD65(96–585) Identifies GAD Autoantibodies That Are More Closely Associated With Diabetes Progression in Relatives of Patients With Type 1 Diabetes

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