Diagnostic accuracy of the anti‐glutamic acid decarboxylase antibody in type 1 diabetes mellitus: Comparison between radioimmunoassay and enzyme‐linked immunosorbent assay

Anti‐glutamic acid decarboxylase antibody ( GADA ) is an important islet cell‐associated autoantibody for the diagnosis of autoimmune type 1 diabetes mellitus. In Japan, the GADA assay kit was recently changed from radioimmunoassay ( RIA ) to enzyme‐linked immunosorbent assay ( ELISA ). Thereafter, a mismatched measurement between the two tests became apparent in clinical situations. The present study aimed to clarify the actual extent of mismatch between the two measurements on a larger‐scale real‐world clinical practice. In this cross‐sectional non‐local/non‐hospital‐based study, we collected anonymized data on GADA levels of 598 participants, who were simultaneously measured with GADA ‐ RIA and GADA enzyme‐linked immunosorbent assay tests. We found that 34% of the GADA ‐ RIA ‐positive participants showed negative results in the GADA enzyme‐linked immunosorbent assay test; the mismatch was predominantly observed in participants with relatively low GADA ‐ RIA levels (<32 U/ mL ). This considerable mismatch might lead to physicians’ confusion in diagnosing type 1 diabetes mellitus.

Section: Resultssupporting

confidence: 85%

Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Actual condition survey regarding mismatch of measurements between radioimmunoassay and enzyme‐linked immunosorbent assay tests for anti‐glutamic acid decarboxylase antibody in real‐world clinical practice

Oikawa

Kondo

Shimada

et al. 2018

“…An example of this is in cases of a single subtype of type 1 diabetes that might not be included in these results, as those patients whose GADA turned positive by modified ELISA protocol consisted of all three subtypes of type 1 diabetes; that is, acute‐onset, fulminant and slowly progressive type 1 diabetes. It has been reported that the GADA titer in RIA(+)/ELISA(−) sera is lower than in RIA(+)/ELISA(+) sera. In general, high‐affinity antibodies bind a greater amount of antigen in a shorter period of time than low‐affinity antibodies.…”

Section: Discussionmentioning

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

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.

“…Recently, measurement of GADA has changed from RIA to non‐radioactive enzyme‐linked immunosorbent assay (GADA‐ELISA) in Japan. This commercially available GADA‐ELISA is reported to have higher specificity for the diagnosis of type 1 diabetes, as compared with GADA‐RIA. However, the correlation between GADA titers, as measured with GADA‐ELISA, and residual β‐cell function has not been fully investigated in patients with type 1 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Circulating anti‐glutamic acid decarboxylase‐65 antibody titers are positively associated with the capacity of insulin secretion in acute‐onset type 1 diabetes with short duration in a Japanese population

Yamamura

Fukui

Mori

et al. 2019

Aims/Introduction To elucidate the relationship between titers of islet autoantibodies, the C‐X‐C motif chemokine 10 – a circulating chemokine that activates T‐helper 1 cells leading to β‐cell destruction – and β‐cell function in type 1 diabetes. Materials and Methods In total, 58 type 1 diabetes patients positive for glutamic decarboxylase‐65 autoantibodies (GADA)‐radioimmunoassay (mean age 54.1 years; 27 acute‐onset cases and 31 slowly progressive cases) were enrolled; serum C‐X‐C motif chemokine 10 (n = 50), zinc transporter 8 autoantibodies (n = 50) and GADA (n = 58) by an enzyme‐linked immunosorbent assay, and insulinoma‐associated antigen‐2 autoantibodies by radioimmunoassay (n = 50) were measured. The ratio of 100 × random C‐peptide (ng/mL)‐to‐plasma glucose levels (mg/dL; C‐peptide index [CPI]) was measured. Results The CPI significantly decreased in both groups with the progression of disease duration. GADA titers by radioimmunoassay and enzyme‐linked immunosorbent assay were strongly correlated with the CPI in acute‐onset type 1 diabetes patients with a shorter disease duration (≤10 years), but not in those with a longer duration or slowly progressive type 1 diabetes. Neither insulinoma‐associated antigen‐2 nor zinc transporter 8 autoantibodies titers were correlated with the CPI. Serum C‐X‐C motif chemokine 10 levels in both groups were significantly higher than in non‐diabetic controls, and persisted at high levels even in those with chronic duration. Conclusions Among islet autoantibodies, the intensity of the humoral immune response, as defined by GADA titers, reflected the degree of residual β‐cell function in acute‐onset type 1 diabetes patients with short duration. Prolonged disease activity might accelerate β‐cell impairment in both subtypes of type 1 diabetes.