Patterns of β-Cell Autoantibody Appearance and Genetic Associations During the First Years of Life
Patterns of β-Cell Autoantibody Appearance and Genetic Associations During the First Years of Life
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DOI：
10.2337/db13-0300
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发表时间：
2013-10-01
期刊：
影响因子：
7.7
通讯作者：
Knip, Mikael
中科院分区：
文献类型：
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作者：
Ilonen, Jorma;Hammais, Anna;Knip, Mikael
我们分析了反映自身免疫过程的各种糖尿病相关自身抗体儿童之间的人口统计学和遗传差异。在一项包含hla易感性1型糖尿病（T1D）儿童的前瞻性出生队列研究中，对520名与疾病高风险相关的晚期细胞自身免疫儿童的自身抗体表现模式进行了分析。315例中，首个阳性样本中可检出单一生化自身抗体为胰岛素（胰岛素自身抗体[IAA]） 180例，GAD (GAD抗体[GADA]) 107例，IA-2抗原（IA-2抗体[IA-2A]） 28例。三组血清转化年龄差异有统计学意义（P = 0.003）。IAA作为第一个自身抗体在出生后的第二年出现高峰，而GADA作为第一个自身抗体在3 - 5岁之间出现高峰。胰岛素相关基因rs689 A/A基因型在以IAA为第一自身抗体的患儿中发生率高于其他患儿（P = 0.002）。在-细胞自身免疫和T1D的发展过程中，原代自身抗原似乎与年龄和遗传因素密切相关，这表明疾病发生过程的异质性。
We analyzed demographic and genetic differences between children with various diabetes-associated autoantibodies reflecting the autoimmune process. In a prospective birth cohort comprising children with HLA-conferred susceptibility to type 1 diabetes (T1D), the pattern of autoantibody appearance was analyzed in 520 children with advanced -cell autoimmunity associated with high risk for disease. In 315 cases, a single biochemical autoantibody could be identified in the first positive sample as insulin (insulin autoantibody [IAA]) in 180, as GAD (GAD antibody [GADA]) in 107, and as IA-2 antigen (IA-2 antibody [IA-2A]) in 28. The age at seroconversion differed significantly between the three groups (P = 0.003). IAA as the first autoantibody showed a peak time of appearance during the second year of life, whereas GADA as the first autoantibody peaked later, between 3 and 5 years of age. The risk-associated insulin gene rs689 A/A genotypes were more frequent in children with IAA as the first autoantibody compared with the other children (P = 0.002). The primary autoantigen in the development of -cell autoimmunity and T1D seems to strongly correlate with age and genetic factors, indicating heterogeneity in the initiation of the disease process.