The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes
The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes
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DOI：
10.1007/s00125-015-3830-2
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发表时间：
2016-03-01
期刊：
影响因子：
8.2
通讯作者：
Krischer, Jeffrey P.
中科院分区：
文献类型：
--
作者：
Bingley, Polly J.;Boulware, David C.;Krischer, Jeffrey P.
针对单一胰岛自身抗原的自身抗体与1型糖尿病的总体风险低于多种自身抗体相关，但具有一种自身抗体的个体可能进展为更高风险类别。我们研究了这种进展的特点，在前瞻性的TrialNet Pathway to Prevention.Methods研究人群包括983名亲属谁是单一自身抗体阳性与正常的基线葡萄糖耐量（中位年龄16.2岁）。对样本进行了GAD、胰岛素瘤相关抗原2（IA-2）和胰岛素抗体筛查，所有阳性样本均进行了锌转运蛋白8抗体和胰岛细胞抗体检测。结果983名亲属中有118名出现了至少一种其他胰岛自身抗原的抗体（总体5年风险22%，95%CI [17.9，26.1]）。在基线时，GAD抗体（68%）比胰岛素抗体（26%）或IA-2抗体（6%）更常见，但所有抗体均与发生其他自身抗体的相似风险相关。风险与年龄较小（p=0.002）和HLA II类基因型相关，但在高和中等遗传风险组中相似（p=0.65）。在随访期间成为多个自身抗体阳性的亲属患糖尿病的风险增加，与研究entry.Conclusions/interpretation胰岛自身免疫的进展在儿童期/成年期的单一自身抗体阳性亲属的风险与自身抗体GAD和一个独特的HLA风险特征的优势。1型糖尿病自身免疫的这种异质性对疾病预防具有潜在的重要意义。
Aims/hypothesis Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention.Methods The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16.2 years). Samples were screened for antibodies to GAD, insulinoma-associated antigen 2 (IA-2) and insulin, and all positive samples tested for antibodies to zinc transporter 8 and islet cell antibodies.Results Antibodies to at least one additional islet autoantigen appeared in 118 of 983 relatives (overall 5 year risk 22%, 95% CI [17.9, 26.1]). At baseline, antibodies to GAD alone (68%) were more frequent than antibodies to insulin (26%) or IA-2 (6%), but all were associated with a similar risk of developing additional autoantibodies. Risk was associated with younger age (p=0.002) and HLA class II genotype, but was similar in high and intermediate genetic risk groups (p=0.65). Relatives who became multiple autoantibody positive during the follow-up had increased risk of developing diabetes comparable with the risk in relatives with multiple autoantibodies at study entry.Conclusions/interpretation Progression of islet autoimmunity in single autoantibody positive relatives in late childhood/adult life is associated with a predominance of autoantibodies to GAD and a distinct HLA risk profile. This heterogeneity in type 1 diabetes autoimmunity has potentially important implications for disease prevention.