Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Diabetes Metab Res Rev. 2011 Nov;27(8):778-83. doi: 10.1002/dmrr.1251.
Our recent review of the literature revealed that approximately 20 antigens are now known to be targeted by T cells in the NOD mouse model of the autoimmune disease type 1 diabetes. Of these, insulin has received considerable attention and has been described by some in the research community as an 'initiating' or 'single major' antigen in the disease. Insulin may indeed be worthy of these titles, at least in NOD mice and in the context of the particular major histocompatibility complex molecules expressed in this strain. However, here we present arguments in favour of viewing type 1 diabetes as a disease in which multiple antigens should be considered, rather than just one. In our view, other antigens may prove to be more worthy of these titles in humans, and the major histocompatibility complex molecules expressed may well be a determining factor. Furthermore, even if insulin is 'the initiating antigen' in type 1 diabetes, multiple pathogenic specificities are known to exist even during the prediabetic period and it is at our peril that we ignore them. The recent discovery of novel beta-cell antigens, e.g. ZnT8 and chromogranin A, has taught us that we still have much to learn about the targets of the autoimmune response in type 1 diabetes. Increased knowledge will promote a clearer picture of disease pathogenesis and will better position the field to be successful in its translational goals of immune monitoring and disease prevention and reversal.
我们最近对文献的回顾表明，目前已知大约有 20 种抗原被 NOD 小鼠自身免疫性 1 型糖尿病模型中的 T 细胞所靶向。在这些抗原中，胰岛素受到了相当多的关注，并且一些研究人员将其描述为该疾病的“起始”或“单一主要”抗原。在 NOD 小鼠和该品系中表达的特定主要组织相容性复合体分子的背景下，胰岛素确实可能配得上这些称号。然而，在这里我们提出了一些观点，即应将 1 型糖尿病视为一种需要考虑多种抗原的疾病，而不仅仅是一种抗原。在我们看来，其他抗原在人类中可能更有资格获得这些称号，而表达的主要组织相容性复合体分子可能是一个决定因素。此外，即使胰岛素是 1 型糖尿病的“起始抗原”，在糖尿病前期甚至也存在多种致病性特异性，而忽视这些特异性则是危险的。最近发现了新的β细胞抗原，例如 ZnT8 和嗜铬粒蛋白 A，这使我们了解到，我们仍然需要更多地了解 1 型糖尿病中自身免疫反应的靶标。更多的知识将有助于更清晰地了解疾病的发病机制，并使该领域更好地实现免疫监测、疾病预防和逆转的转化目标。
