Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation.
Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation.
复制标题
糖尿病前期的早期自身抗体反应以 IgG1 为主，提示抗原特异性调节。
DOI：
10.4049/jimmunol.163.1.525
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发表时间：
1999
影响因子：
4.4
通讯作者：
A. Ziegler
中科院分区：
文献类型：
--
作者：
E. Bonifacio;M. Scirpoli;K. Kredel;M. Füchtenbusch;A. Ziegler
临床前1型糖尿病的胰岛自身免疫在人类中的特征仍然很差。在本文中，IgG亚类反应的胰岛自身抗原胰岛素，谷氨酸脱羧酶，IA-2的顺序进行了研究，从出生到糖尿病发病或目前的后续在26个自身抗体阳性的后代的父母患有糖尿病。胰岛自身抗体出现的特征是对一种或多种抗原（最常见的是胰岛素）的早期IgG 1峰反应，中位年龄为2.2岁（四分位距，2-2.9岁）。在五个后代，急性暴发性β细胞破坏和糖尿病发作发生在这个初始抗体反应。在其余的，早期抗体水平显着下降，并针对其他β细胞抗原的抗体峰连续出现了几年，表明自身免疫的调节和传播。仅在两个后代中观察到对相同Ag的第二峰Ab反应，这两个后代此时都患有糖尿病。另外两人患上了糖尿病，抗体水平下降。抗体的IgG 1亚类占主导地位，对每个抗原，和其他亚类，通常只检测到峰值IgG 1反应。IgG 4对胰岛素的反应异常，在四只后代中比IgG 1占主导地位，在另外五只后代中，IgG 1水平下降后出现和/或持续存在。这些Th 2相关的IgG 4应答与糖尿病保护无关。对DA 2的IgG 1限制性反应的存在与糖尿病的发展相关。这些发现表明，1型糖尿病具有β细胞自身免疫的早期急性破坏性阶段，其可以被调节并且慢性传播直到糖尿病发作。
The islet autoimmunity of preclinical type 1 diabetes remains poorly characterized in humans. In this paper, the IgG subclass response to the islet autoantigens insulin, glutamic acid decarboxylase, and IA-2 was studied sequentially from birth to diabetes onset or current follow-up in 26 autoantibody positive offspring of parents with diabetes. Islet autoantibody appearance was characterized by an early IgG1 peak response to one or more Ags, most commonly to insulin, at a median age of 2.2 yr (interquartile range, 2-2.9 yr). In five offspring, an acute fulminant beta-cell destruction and diabetes onset occurred during this initial Ab response. In the remainder, early Ab levels declined markedly, and Ab peaks against other beta cell Ags arose sequentially over several years suggesting regulation and spreading of autoimmunity. Second peak Ab responses to the same Ag were observed in only two offspring, both developing diabetes at this time. Two others developed diabetes with declining Ab levels. Abs of IgG1 subclass dominated against each Ag, and other subclasses, were usually only detected during peak IgG1 responses. The IgG4 response to insulin was exceptional, being dominant over IgG1 in four offspring and in five others appeared and/or persisted after IgG1 levels declined. These Th2-associated IgG4 responses were not correlated with protection from diabetes. The presence of IgG1-restricted responses to DA2 were associated with diabetes development. These findings suggest that type 1 diabetes has an early acute destructive phase of beta cell autoimmunity, which may be regulated and which spreads chronically until diabetes onset.