Congenital beta cell defects are not associated with markers of islet autoimmunity, even in the context of high genetic risk for type 1 diabetes.
Congenital beta cell defects are not associated with markers of islet autoimmunity, even in the context of high genetic risk for type 1 diabetes.
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先天性β细胞缺陷与胰岛自身免疫标志物无关，即使在1型糖尿病遗传风险高的背景下。
DOI：
10.1007/s00125-022-05697-3
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发表时间：
2022-07
期刊：
影响因子：
8.2
通讯作者：
Johnson, Matthew B.
中科院分区：
文献类型：
--
作者：
Wyatt, Rebecca C.;Hagopian, William A.;Roep, Bart O.;Patel, Kashyap A.;Resnick, Brittany;Dobbs, Rebecca;Hudson, Michelle;De Franco, Elisa;Ellard, Sian;Flanagan, Sarah E.;Hattersley, Andrew T.;Oram, Richard A.;Johnson, Matthew B.
1型糖尿病中一个关键的未回答的问题是β细胞是否启动了自身的破坏或成为异常免疫反应的受害者（β细胞自杀或杀人？）。为了研究这一点，我们评估了导致新生儿糖尿病（NDM）的先天性β细胞缺陷个体的胰岛自身抗体。我们检测了242例NDM患者的GADA、IA-2A和ZnT 8A自身抗体（中位诊断年龄1.8个月[IQR 0.39-2.9个月];中位收集年龄4.6个月[IQR 1.8-27.6个月];中位糖尿病持续时间2个月[IQR 0.6-23个月]），包括75例严重β细胞内质网（ER）应激导致的NDM。作为对照组，我们还检测了来自69名无糖尿病个体（收集的中位年龄为9.9个月[IQR 9.0-48.6个月]）的自身抗体样本。我们发现单基因NDM患者胰岛自身抗体的患病率较低; 13/242（5.4% [95% CI 2.9，9.0%]）可检测到GADA、IA-2A和/或ZnT 8A。这与未患糖尿病的对照参与者的比例相似（1/69阳性[1.4%，95% CI 0.03，7.8%]，p=0.3）。重要的是，具有β细胞ER应激的单基因个体具有与非ER应激病因相似的GADA/IA-2A/ZnT 8A阳性率（2.7% [95%CI 0.3，9.3%] vs 6.6% [95%CI 3.3，11.5%] p=0.4）。我们没有观察到胰岛自身免疫与遗传风险、测试时年龄（包括30名测试时>10岁的个体）或糖尿病病程（所有患者p>0.4）之间存在关联。我们的数据支持这一假设，即β细胞应激/功能障碍单独不会导致胰岛自身抗体的产生，即使在高危HLA类型的背景下。这表明需要额外的因素来触发对β细胞的自身免疫反应。在线版本包含同行评审但未经编辑的补充材料，可通过10.1007/s 00125 -022-05697-3获得。
A key unanswered question in type 1 diabetes is whether beta cells initiate their own destruction or are victims of an aberrant immune response (beta cell suicide or homicide?). To investigate this, we assessed islet autoantibodies in individuals with congenital beta cell defects causing neonatal diabetes mellitus (NDM). We measured autoantibodies to GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) in 242 individuals with NDM (median age diagnosed 1.8 months [IQR 0.39–2.9 months]; median age collected 4.6 months [IQR 1.8–27.6 months]; median diabetes duration 2 months [IQR 0.6–23 months]), including 75 whose NDM resulted from severe beta cell endoplasmic reticulum (ER) stress. As a control cohort we also tested samples from 69 diabetes-free individuals (median age collected 9.9 months [IQR 9.0–48.6 months]) for autoantibodies. We found low prevalence of islet autoantibodies in individuals with monogenic NDM; 13/242 (5.4% [95% CI 2.9, 9.0%]) had detectable GADA, IA-2A and/or ZnT8A. This was similar to the proportion in the control participants who did not have diabetes (1/69 positive [1.4%, 95% CI 0.03, 7.8%], p=0.3). Importantly, monogenic individuals with beta cell ER stress had a similar rate of GADA/IA-2A/ZnT8A positivity to non-ER stress aetiologies (2.7% [95% CI 0.3, 9.3%] vs 6.6% [95% CI 3.3, 11.5%] p=0.4). We observed no association between islet autoimmunity and genetic risk, age at testing (including 30 individuals >10 years at testing) or diabetes duration (p>0.4 for all). Our data support the hypothesis that beta cell stress/dysfunction alone does not lead to the production of islet autoantibodies, even in the context of high-risk HLA types. This suggests that additional factors are required to trigger an autoimmune response towards beta cells. The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-022-05697-3.
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影响因子：
16.2
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