Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
Diabetes Care. 2018 May;41(5):1076-1083. doi: 10.2337/dc17-2462. Epub 2018 Mar 15.
We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes.
A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity ( = 267) and from multiple-autoantibody positivity to clinical onset ( = 252) according to , , , and status. Genetic markers were determined by PCR sequence-specific oligotyping.
Unlike or , was associated with delayed progression from single- to multiple-autoantibody positivity ( = 0.009) but not to type 1 diabetes. This occurred independently from older age ( < 0.001) and absence of or < 0.001 and = 0.003, respectively), and only in the presence of GAD autoantibodies. In contrast, was associated with accelerated progression from multiple-autoantibody positivity to clinical onset ( = 0.006), but its effects were restricted to relatives with IA-2 or zinc transporter 8 autoantibodies ( = 0.002). but not was also associated with more rapid progression, but only in carriers with double positivity for GAD and insulin autoantibodies ( = 0.004).
predisposes to a delayed antigen spreading of humoral autoimmunity, whereas and are associated with accelerated progression of advanced subclinical autoimmunity in distinct risk groups. The relation of these alleles to the underlying disease process requires further investigation. Their typing should be relevant for the preparation and interpretation of observational and interventional studies in asymptomatic type 1 diabetes.
我们研究了 HLA I 类风险等位基因对 1 型糖尿病患者一级亲属亚临床胰岛自身免疫不同阶段疾病进展的影响。
根据、、、和状态，我们从单阳性到多阳性（=267）和从多阳性到临床发病（=252）对基于登记的同胞/子女（年龄 0-39 岁）进行监测。通过 PCR 序列特异性寡核苷酸分型确定遗传标记。
与或不同，与从单阳性到多阳性的进展延迟相关（=0.009），但与 1 型糖尿病无关。这与年龄较大（<0.001）和缺乏或（<0.001 和=0.003，分别）独立发生，仅在存在 GAD 自身抗体的情况下发生。相比之下，与从多阳性到临床发病的进展加速相关（=0.006），但其作用仅限于 IA-2 或锌转运体 8 自身抗体阳性的亲属（=0.002）。但不是也与更快的进展相关，但仅在 GAD 和胰岛素自身抗体双重阳性的携带者中（=0.004）。
易发生体液自身免疫的抗原扩散延迟，而和则与特定风险群体中晚期亚临床自身免疫的加速进展相关。这些等位基因与潜在疾病过程的关系需要进一步研究。它们的分型应与无症状 1 型糖尿病的观察性和干预性研究的准备和解释相关。
