Université Paris Descartes, 75015 Paris, France.
Semin Immunol. 2011 Jun;23(3):174-81. doi: 10.1016/j.smim.2011.07.009. Epub 2011 Aug 16.
Type 1 diabetes is an autoimmune disease. It was thus logical to attempt preventing or stopping the progression of the disease by immunotherapy. Following the strategies used in organ transplantation, the first trials in the 80s used cyclosporin in patients presenting recently diagnosed Type 1 diabetes. The effect was spectacular but waned when the treatment was stopped as the effect was non antigen-specific. Going back from bed to bench-side major efforts were then devoted to device strategies allowing induction or restoration of self-tolerance. Two major approaches provided encouraging results when used in spontaneous models of autoimmune diabetes that are the use of β-cell autoantigens and of monoclonal antibodies to CD3. Based on these results academic phase II trials and subsequently pharmaceutically driven phase III trials were launched. Results are now available and when critically analyzed in the frame of these last three decades they provide support to the possibility of making step by step immunotherapy available to all new onset diabetic patients with a hope of inducing long-term remission of the disease if the treatment is started sufficiently early, immediately after diagnosis.
1 型糖尿病是一种自身免疫性疾病。因此，通过免疫疗法来预防或阻止疾病的进展是合乎逻辑的。借鉴器官移植中使用的策略，80 年代的首次试验在近期被诊断为 1 型糖尿病的患者中使用环孢菌素。当治疗停止时，效果非常显著，但效果逐渐消失，因为这种效果是非抗原特异性的。随后，人们从临床回到实验室，致力于开发诱导或恢复自身耐受的设备策略。在自身免疫性糖尿病的自发性模型中，两种主要方法的应用取得了令人鼓舞的结果，即使用β细胞自身抗原和抗 CD3 单克隆抗体。基于这些结果，开展了学术性的 II 期临床试验，随后又开展了制药驱动的 III 期临床试验。现在已经有了结果，在过去三十年的框架内进行批判性分析时，这些结果为逐步为所有新诊断的糖尿病患者提供免疫疗法的可能性提供了支持，如果治疗足够早，即在诊断后立即开始，那么有希望诱导疾病的长期缓解。
