Institute of Biomedical & Clinical Science, University of Exeter Medical School, Exeter, Devon EX2 5DW, UK.
Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London SW7 2AZ, UK.
J Clin Endocrinol Metab. 2022 Nov 25;107(12):e4341-e4349. doi: 10.1210/clinem/dgac507.
The importance of the autoantibody level at diagnosis of type 1 diabetes (T1D) is not clear.
We aimed to assess the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) autoantibody levels with clinical and genetic characteristics at diagnosis of T1D.
We conducted a prospective, cross-sectional study. GADA, IA-2A, and ZnT8A were measured in 1644 individuals with T1D at diagnosis using radiobinding assays. Associations between autoantibody levels and the clinical and genetic characteristics for individuals were assessed in those positive for these autoantibodies. We performed replication in an independent cohort of 449 people with T1D.
GADA and IA-2A levels exhibited a bimodal distribution at diagnosis. High GADA level was associated with older age at diagnosis (median 27 years vs 19 years, P = 9 × 10-17), female sex (52% vs 37%, P = 1 × 10-8), other autoimmune diseases (13% vs 6%, P = 3 × 10-6), and HLA-DR3-DQ2 (58% vs 51%, P = .006). High IA-2A level was associated with younger age of diagnosis (median 17 years vs 23 years, P = 3 × 10-7), HLA-DR4-DQ8 (66% vs 50%, P = 1 × 10-6), and ZnT8A positivity (77% vs 52%, P = 1 × 10-15). We replicated our findings in an independent cohort of 449 people with T1D where autoantibodies were measured using enzyme-linked immunosorbent assays.
Islet autoantibody levels provide additional information over positivity in T1D at diagnosis. Bimodality of GADA and IA-2A autoantibody levels highlights the novel aspect of heterogeneity of T1D. This may have implications for T1D prediction, treatment, and pathogenesis.
1 型糖尿病（T1D）诊断时自身抗体水平的重要性尚不清楚。
我们旨在评估谷氨酸脱羧酶（GADA）、胰岛抗原 2（IA-2A）和锌转运体 8（ZnT8A）自身抗体水平与 T1D 诊断时临床和遗传特征的相关性。
我们进行了一项前瞻性、横断面研究。使用放射结合测定法在 1644 名 T1D 患者中检测了 GADA、IA-2A 和 ZnT8A。在这些自身抗体阳性的个体中，评估了自身抗体水平与个体临床和遗传特征之间的关系。我们在另一个独立的 449 名 T1D 患者队列中进行了复制。
GADA 和 IA-2A 水平在诊断时呈双峰分布。高 GADA 水平与诊断时年龄较大（中位数 27 岁比 19 岁，P = 9×10-17）、女性（52%比 37%，P = 1×10-8）、其他自身免疫性疾病（13%比 6%，P = 3×10-6）和 HLA-DR3-DQ2（58%比 51%，P =.006）相关。高 IA-2A 水平与诊断时年龄较小（中位数 17 岁比 23 岁，P = 3×10-7）、HLA-DR4-DQ8（66%比 50%，P = 1×10-6）和 ZnT8A 阳性（77%比 52%，P = 1×10-15）相关。我们在另一个独立的 449 名 T1D 患者队列中使用酶联免疫吸附测定法测量自身抗体时复制了我们的发现。
胰岛自身抗体水平在 T1D 诊断时提供了比阳性更有价值的信息。GADA 和 IA-2A 自身抗体水平的双峰性突出了 T1D 异质性的新方面。这可能对 T1D 的预测、治疗和发病机制有影响。
