Clinical and genetic characteristics of people with type 1 diabetes who have discrepancies in titers of anti‐glutamic acid decarboxylase antibody measured by radioimmunoassay and enzyme‐linked immunosorbent assay

Abstract

Aims/Introduction The aim of the present study was to compare the clinical and genetic characteristics between people with type 1 diabetes who were positive and negative for autoantibodies against glutamic acid decarboxylase (GADA) measured by enzyme‐linked immunosorbent assay (ELISA) with low‐titer GADA measured by radioimmunoassay. Materials and Methods Among Japanese people with type 1 diabetes in whom GADA were measured by both ELISA and radioimmunoassay, those who had low titers of GADA measured by radioimmunoassay (1.5–10 U/mL), regardless of positivity for GADA measured by ELISA, were studied. There were 65 participants with acute‐onset type 1 diabetes and 30 participants with slowly progressive insulin‐dependent diabetes mellitus. Clinical characteristics and human leukocyte antigen types were compared in ELISA‐positive (≥5 U/mL) and ELISA‐negative participants. Endogenous insulin secretion was evaluated by C‐peptide index. Results Among participants with slowly progressive insulin‐dependent diabetes mellitus, postprandial C‐peptide index was significantly higher in ELISA‐negative participants than in ELISA‐positive participants (r = 0.619, P = 0.002). Among 52 participants whose human leukocyte antigen typing was carried out, all of the participants with slowly progressive insulin‐dependent diabetes mellitus who had DRB1*09:01 were positive by GADA‐ELISA (P = 0.021). In acute‐onset type 1 diabetes participants, there were no significant differences for the C‐peptide index and human leukocyte antigen genotypes. Conclusions The difference in the positivity for GADA‐ELISA might reflect cytotoxicity toward pancreatic β‐cells and preservation of endogenous insulin secretion in people with slowly progressive insulin‐dependent diabetes mellitus. We also suggest that the difference in the GADA‐ELISA‐specific epitope depends on the human leukocyte antigen genotype.

Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association With Genetic and Clinical Characteristics

“…S2) ( 11 ). This was also in line with previous studies ( 39 , 40 ). This suggests that our findings are applicable to levels measured by both methods.…”

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“…Among the cases originally diagnosed as SPIDDM by the GAD‐RIA method, the GAD‐ELISA‐positive cases had significantly lower C‐peptide levels than the GAD‐ELISA‐negative cases 12 . Even in 30 SPIDDM cases with an anti‐GAD‐RIA antibody titer of ≤10 U/mL, the C‐peptide values were significantly lower in the GAD‐ELISA‐positive cases than in the negative cases, and HLA‐DR9(+) cases were significantly more common among positive cases ( P < 0.05) 13 . On the other hand, the method for detection of anti‐IA‐2 antibody was also changed from the RIA to ELISA in October 2018, and similar differences between the two methods were examined.…”

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“…6 Today, the methods to detecting GPC3 concentration include fluorescence immunoassay, bioluminescence enzyme immunoassay, radioimmunoassay, enzyme-linked immunosorbent assay and electrochemical immunoassay. [7][8][9] These traditional detection techniques usually have the advantages of high sensitivity and accuracy, but the disadvantages are high cost and complicated processing methods. In addition, the high price, long preparation time and strict storage conditions of the recognition molecules (antibodies) required for these detections make the GPC3 detection unable to meet its requirements.…”