Insulin autoimmunity Immunogenetics/immunopathogenesis of type 1A diabetes
Insulin autoimmunity Immunogenetics/immunopathogenesis of type 1A diabetes
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DOI：
10.1196/annals.1288.012
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发表时间：
2003-01-01
期刊：
影响因子：
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通讯作者：
Eisenbarth, GS
中科院分区：
文献类型：
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作者：
Eisenbarth, GS
我们现在可以预测人类1A型糖尿病的发展，并在动物模型中预防这种疾病，但我们目前还不能安全地预防人类1A型糖尿病，尽管一系列的临床试验正在进行和计划中。我们目前的试验设计的一个主要缺陷是无法测量直接负责细胞破坏的T淋巴细胞。鉴于1A型糖尿病的免疫遗传学和NOD小鼠发病机制的不断增加的知识，我们认为这种疾病是由于对一组有限的胰岛肽的免疫反应性造成的，而对胰岛素的反应性是疾病的主要决定因素。胰岛素自身抗体先于人类和NOD小鼠的糖尿病发展。从NOD小鼠胰岛分离出识别胰岛素肽B:9-23的T淋巴细胞可转移糖尿病。胸腺内的胰岛素表达与遗传易感性相关，胰岛素肽可用于诱导糖尿病，也可作为预防糖尿病的免疫疫苗。然而，目前抗胰岛素T淋巴细胞的常规检测还不规范。更好地监测这种自身反应性的检测方法可能对预防疗法的开发和评价至关重要。
We can now predict the development of type 1A diabetes in humans and prevent the disorder in animal models, but we cannot at present safely prevent type 1A diabetes in humans, although a series of clinical trials are under way and planned. A major lack in our current trial design is the inability to measure T lymphocytes directly responsible for beta cell destruction. Given the immunogenetics of type 1A diabetes and increasing knowledge of pathogenesis in the NOD mouse, we believe the disorder results from immune reactivity to a limited set of islet peptides, with reactivity to insulin a major determinant of disease. Insulin autoantibodies precede the development of diabetes in both humans and the NOD mouse. T lymphocytes isolated from the islets of the NOD mouse that recognize insulin peptide B:9-23 can transfer diabetes. Insulin expression within the thymus is correlated with genetic susceptibility, and insulin peptides can be used to induce diabetes and as an immunologic vaccine to prevent the disorder. Nevertheless, at present, routine measurement of anti-insulin T lymphocytes is not standardized. Better assays to monitor such autoreactivity are likely to be essential for the development and evaluation of preventive therapies.