Analysis of the GAD65–GAD65 autoantibody interaction

Coco, Graziella; Shu, Chen; Powell, Michael J.; Brooking, Helen; Zanchetta, R.; Betterle, Corrado; Smith, Bernard Rees; Furmaniak, Jadwiga

doi:10.1016/j.cca.2008.02.005

Cited by 2 publications

(2 citation statements)

References 28 publications

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“…We have previously shown that GADA responses in nondiabetic children with first-degree family history of type 1 diabetes can be heterogeneous with respect to affinity and epitope specificity and that diabetes development in these children is associated with high-affinity GADAs (11), suggesting that only mature autoantibody responses have disease relevance. Concordantly, high-affinity GADAs have been found in patients with type 1 diabetes (16). We also described a type of autoantibody response with a stunted maturation and limited progression to other islet antigens, which was unrelated to type 1 diabetes development (11).…”

Section: Discussionmentioning

confidence: 55%

GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial

Krause

Landherr²,

Agardh

et al. 2014

Diabetes Care

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Section: Discussionmentioning

confidence: 55%

GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial

Krause

Landherr²,

Agardh

et al. 2014

Diabetes Care

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“…Half‐maximal inhibitory concentration (IC50) and Kd values were calculated by non‐linear regression analysis using SigmaPlot version 14.0 software (Systat Software Inc., San Jose, CA, USA). Kd values were determined using the dissociation constants in GADA‐positive patients and ligand concentration for each assay. GADA affinity was expressed as reciprocal Kd value (L/mol).…”

Section: Methodsmentioning

confidence: 99%

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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Analysis of the GAD65–GAD65 autoantibody interaction

Cited by 2 publications

References 28 publications

GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial

GAD Autoantibody Affinity in Adult Patients With Latent Autoimmune Diabetes, the Study Participants of a GAD65 Vaccination Trial

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

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