1型糖尿病风险增加儿童的胰岛自身抗体表型及发病率
Islet autoantibody phenotypes and incidence in children at increased risk for type 1 diabetes.
作者信息
Giannopoulou Eleni Z, Winkler Christiane, Chmiel Ruth, Matzke Claudia, Scholz Marlon, Beyerlein Andreas, Achenbach Peter, Bonifacio Ezio, Ziegler Anette-G
机构信息
Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.
Forschergruppe Diabetes e.V., Neuherberg, Germany.
出版信息
Diabetologia. 2015 Oct;58(10):2317-23. doi: 10.1007/s00125-015-3672-y. Epub 2015 Jul 3.
AIMS/HYPOTHESIS: Autoantibodies that precede type 1 diabetes frequently develop in early childhood and target distinct beta cell proteins. The aim of this study was to determine the heterogeneity of islet autoantibody development and fate.
METHODS
The ages of development of insulin autoantibodies (IAA) and GAD autoantibodies (GADA), followed by multiple islet autoantibodies and progression to diabetes were examined in 2,441 children participating in two German birth cohorts.
RESULTS
In 218 children who developed islet autoantibodies, the first islet autoantibody-positive sample was characterised by single IAA in 80 (37%), multiple islet autoantibodies in 68 (31%) and single GADA in 63 (29%) children. Of the children who were single antibody positive at seroconversion, 35 (44%) IAA-positive and 15 (24%) GADA-positive children developed multiple islet autoantibodies. Single persistent antibodies had heterogeneous affinities; GADA were also heterogeneous in their binding to N-terminally truncated GAD65 and in an ELISA. Progression to diabetes occurred in >50% of children within 10 years in all groups that developed multiple islet autoantibodies and in 44% of children with persistent single high-affinity IAA or persistent single GADA that were positive in both a radiobinding assay and ELISA. The earliest autoantibody development was seen in children with single IAA that progressed to multiple islet autoantibodies or in those with persistent high-affinity single IAA, with a sharp peak in incidence observed at age 9 months. The peak incidence occurred at age 2 years for children who underwent seroconversion directly to multiple islet autoantibodies and at 5 years for children who first seroconverted to GADA and subsequently developed other autoantibodies. Seroconversion to low-affinity IAA or persistent single GADA occurred at a low incidence after the age of 9 months.
CONCLUSIONS/INTERPRETATION: Children of different ages have differing susceptibilities to autoimmunisation against specific beta cell autoantigens.
目的/假设：1型糖尿病前期的自身抗体通常在儿童早期出现，并靶向不同的β细胞蛋白。本研究的目的是确定胰岛自身抗体产生和转归的异质性。
方法
在参与两个德国出生队列研究的2441名儿童中，检测了胰岛素自身抗体（IAA）和谷氨酸脱羧酶自身抗体（GADA）的出现年龄，随后检测了多种胰岛自身抗体以及进展为糖尿病的情况。
结果
在218名出现胰岛自身抗体的儿童中，首次胰岛自身抗体阳性样本的特征为：80名（37%）儿童为单一IAA阳性，68名（31%）儿童为多种胰岛自身抗体阳性，63名（29%）儿童为单一GADA阳性。在血清转化时单一抗体阳性的儿童中，35名（44%）IAA阳性儿童和15名（24%）GADA阳性儿童发展为多种胰岛自身抗体。单一持续性抗体具有异质性亲和力；GADA在与N端截短的GAD65结合以及在酶联免疫吸附测定（ELISA）中也具有异质性。在所有发展为多种胰岛自身抗体的组中，超过50%的儿童在10年内进展为糖尿病，在放射性结合测定和ELISA中均呈阳性的持续性单一高亲和力IAA或持续性单一GADA阳性的儿童中，这一比例为44%。最早出现自身抗体的情况见于进展为多种胰岛自身抗体的单一IAA阳性儿童或持续性高亲和力单一IAA阳性儿童，在9个月时发病率出现急剧峰值。直接血清转化为多种胰岛自身抗体的儿童发病率峰值出现在2岁，首次血清转化为GADA并随后出现其他自身抗体的儿童发病率峰值出现在5岁。9个月龄后，血清转化为低亲和力IAA或持续性单一GADA的发生率较低。
结论/解读：不同年龄的儿童对特定β细胞自身抗原的自身免疫易感性不同。
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