Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
J Diabetes Investig. 2020 Mar;11(2):356-362. doi: 10.1111/jdi.13111. Epub 2019 Aug 1.
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.
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.
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.
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.
目的/引言：本研究旨在比较通过酶联免疫吸附试验（ELISA）检测谷氨酸脱羧酶（GADA）抗体阳性和阴性的 1 型糖尿病患者与通过放射免疫分析检测低滴度 GADA 的临床和遗传特征。
在通过 ELISA 和放射免疫分析检测 GADA 的日本 1 型糖尿病患者中，研究了那些通过放射免疫分析检测 GADA 低滴度（1.5-10 U/mL）的患者，无论 ELISA 检测 GADA 是否阳性。共有 65 名急性发作 1 型糖尿病患者和 30 名缓慢进展性胰岛素依赖型糖尿病患者。比较了 ELISA 阳性（≥5 U/mL）和 ELISA 阴性患者的临床特征和人类白细胞抗原类型。通过 C 肽指数评估内源性胰岛素分泌。
在缓慢进展性胰岛素依赖型糖尿病患者中，ELISA 阴性患者的餐后 C 肽指数显著高于 ELISA 阳性患者（r=0.619，P=0.002）。在进行人类白细胞抗原分型的 52 名患者中，所有缓慢进展性胰岛素依赖型糖尿病患者的 DRB1*09:01 均为 GADA-ELISA 阳性（P=0.021）。在急性发作 1 型糖尿病患者中，C 肽指数和人类白细胞抗原基因型无显著差异。
GADA-ELISA 阳性率的差异可能反映了对胰腺β细胞的细胞毒性和缓慢进展性胰岛素依赖型糖尿病患者内源性胰岛素分泌的保留。我们还表明，GADA-ELISA 特异性表位的差异取决于人类白细胞抗原基因型。
