The first signs of B-cell autoimmunity appear in infancy in genetically susceptible children from the general population:: The Finnish Type 1 Diabetes Prediction and Prevention Study
The first signs of B-cell autoimmunity appear in infancy in genetically susceptible children from the general population:: The Finnish Type 1 Diabetes Prediction and Prevention Study
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DOI：
10.1210/jc.86.10.4782
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发表时间：
2001-10-01
影响因子：
5.8
通讯作者：
Knip, M
中科院分区：
文献类型：
--
作者：
Kimpim채ki, T;Kupila, A;Knip, M
在一般人群中，发病时间和1型糖尿病的临床前过程尚不清楚。在这项基于人群的前瞻性出生队列研究中，从出生开始监测糖尿病相关自身抗体的出现，作为β细胞自身免疫的标志和I型糖尿病的发展。在25,983名新生儿中，2448名遗传易感儿童每隔3至6个月监测一次胰岛细胞抗体（ICA）。如果婴儿血清转化为ICA阳性，还分析其所有样品的胰岛素自身抗体（IAA）， 65-kDa谷氨酸脱羧酶异构体抗体，蛋白酪氨酸磷酸酶相关IA-2分子抗体。携带高危基因型的15名儿童（2.7%）和携带中度风险基因型的23名儿童（1.2%;P = 0.019）至少一次检测出ICA阳性。在观察期内至少有2种抗体阳性的患儿中（38例中有25例），IAA作为第一抗体或第一抗体出现的患儿有22例（88%），且出现时间早于其他抗体（P < 0.019）。第一次自身抗体出现在秋季和冬季的儿童居多（38例中有30例，春、夏季有8例，P < 0.001）。这些观察结果表明，在一般人群中，具有强人类白细胞抗原- dq定义的1型糖尿病遗传风险的幼儿比具有中等遗传风险的幼儿更常显示出β细胞自身免疫的迹象。IAA作为第一个可检测到的抗体比任何其他抗体特异性更常见，这意味着胰岛素可能是大多数与DR4-DQB1*0302单倍型相关的人类1型糖尿病病例的主要抗原。出现β细胞自身免疫最初迹象的季节变化表明，感染因子可能在诱导这种自身免疫中起作用。
Little is known about the timing of the etiological events and the preclinical process of type 1 diabetes during the first years of life in the general population. In this population-based prospective birth cohort study, the appearance of diabetes-associated autoantibodies as a sign of beta -cell autoimmunity and the development of type I diabetes were monitored from birth. Of 25,983 newborn infants, 2,448 genetically susceptible children were monitored for islet cell antibodies (ICA) at 3- to 6-month intervals. If an infant seroconverted to ICA positivity, all his/her samples were also analyzed for insulin autoantibodies (IAA), antibodies to the 65-kDa isoform of glutamic acid decarboxylase, and antibodies to the protein tyrosine phosphatase-related IA-2 molecule. Fifteen children of those who carried the high-risk genotype (2.7%) and 23 of those who carried the moderate-risk genotype (1.2%; P = 0.019) tested positive for ICA at least once. Among those who showed positivity for at least 2 antibodies during the observation period (25 of 38), IAA appeared as the first or among the first antibodies in 22 children (88%) and emerged earlier than the other antibodies (P < 0.019 or less). The first autoantibodies appeared in the majority of the children in the fall and winter (30 of 38 vs. 8 of 38 in the spring and summer, P < 0.001). These observations suggest that young children in the general population with a strong human-leukocyte-antigen-DQ-defined genetic risk of type 1 diabetes show signs of beta -cell autoimmunity proportionally more often than those with a moderate genetic risk. IAA emerge as the first detectable antibody more commonly than any other antibody specificity, implying that insulin may be the primary antigen in most cases of human type 1 diabetes associated with the DR4-DQB1*0302 haplotype. The seasonal variation in the emergence of the first signs of beta -cell autoimmunity suggests that infectious agents may play a role in the induction of such autoimmunity.