Department of General Surgery, Visceral, Thoracic and Vascular Surgery, University Medical Center Greifswald, Greifswald, Germany.
Diabetes Research Institute (SR-DRI), IRCCS Ospedale San Raffaele, Milan, Italy.
Diabet Med. 2021 Feb;38(2):e14389. doi: 10.1111/dme.14389. Epub 2020 Nov 28.
To evaluate the diagnostic relevance of autoantibodies against zinc transporter 8 (ZnT8) in schoolchildren from the general population as well as in people with autoimmune diabetes.
A total of 137 schoolchildren positive for at least one of the three major diabetes-associated autoantibodies, without diabetes heredity or preselection on HLA typing, from the Karlsburg Type 1 Diabetes Risk Study, as well as 102 people at type 1 diabetes onset, 88 people with latent autoimmune diabetes in adults and 119 people with type 2 diabetes, were analysed for different ZnT8 autoantibody variants.
Zinc transporter 8 autoantibody positivity was found in 18% of autoantibody-positive schoolchildren, with a noticeable association with other autoantibodies associated with type 1 diabetes and disease progression. Furthermore, ZnT8 autoantibody positivity was associated with diabetes progression in schoolchildren positive for autoantibodies against insulinoma-associated antigen-2 (IA-2) and, importantly, in seven IA-2 autoantibody-negative schoolchildren. Additionally, ZnT8 autoantibodies were found in 56% of people with type 1 diabetes, predominantly directed against all three ZnT8 variants and comparable to schoolchildren with multiple autoantibodies. In contrast, ZnT8 autoantibodies were detected in 10% of people with latent autoimmune diabetes in adults, none of them with reactivity to all three isoforms.
Zinc transporter 8 autoantibodies are useful markers for prediction of type 1 diabetes in a general population, further stratifying the risk of progression in autoantibody-positive children. ZnT8 autoantibodies are also important markers in adult-onset diabetes, with a completely different reaction pattern in type 1 diabetes in comparison to latent autoimmune diabetes in adults, and may therefore help to differentiate between the two forms.
评估针对锌转运蛋白 8（ZnT8）的自身抗体在普通人群中的儿童以及自身免疫性糖尿病患者中的诊断相关性。
我们分析了来自 Karlsburg 1 型糖尿病风险研究的 137 名至少有一种三种主要糖尿病相关自身抗体阳性的儿童，这些儿童没有糖尿病遗传或 HLA 分型预选，以及 102 名 1 型糖尿病发病患者、88 名成人隐匿性自身免疫性糖尿病患者和 119 名 2 型糖尿病患者，以分析不同 ZnT8 自身抗体变体。
在自身抗体阳性的儿童中，发现 18%存在锌转运蛋白 8 自身抗体阳性，与其他与 1 型糖尿病和疾病进展相关的自身抗体明显相关。此外，ZnT8 自身抗体阳性与对胰岛素瘤相关抗原-2（IA-2）自身抗体阳性的儿童的糖尿病进展相关，重要的是，在 7 名 IA-2 自身抗体阴性的儿童中也是如此。此外，在 56%的 1 型糖尿病患者中发现了 ZnT8 自身抗体，主要针对所有三种 ZnT8 变体，与具有多种自身抗体的儿童相当。相比之下，在成人隐匿性自身免疫性糖尿病患者中仅检测到 10%的 ZnT8 自身抗体，他们均无对所有三种同工型的反应性。
ZnT8 自身抗体是普通人群中预测 1 型糖尿病的有用标志物，可进一步分层自身抗体阳性儿童的进展风险。ZnT8 自身抗体也是成年发病型糖尿病的重要标志物，与成人隐匿性自身免疫性糖尿病相比，在 1 型糖尿病中具有完全不同的反应模式，因此可能有助于区分这两种形式。
