Bone Robert N, Evans-Molina Carmella
Department of Medicine, Indiana School of Medicine, 635 Barnhill Dr, MS 2031A, Indianapolis, IN, 46202, USA.
Center for Diabetes & Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Curr Diab Rep. 2017 Jul;17(7):50. doi: 10.1007/s11892-017-0878-z.
Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D.
Combination immunotherapies have had mixed results in improving short-term glycemic control and insulin secretion in recent-onset T1D. A handful of studies have successfully reached their primary end-point of improved insulin secretion in recent-onset T1D. However, long-term improvements glycemic control and the restoration of insulin independence remain elusive. Future interventions should focus on strategies that combine immunomodulation with efforts to alleviate β-cell stress and address the formation of antigens that activate autoimmunity.
1型糖尿病（T1D）是一种以β细胞破坏为特征的自身免疫性疾病。自20世纪80年代以来，人们一直在研究T1D的免疫疗法，重点是恢复耐受性、抑制T细胞或B细胞、诱导调节性T细胞（Treg）、抑制先天免疫和炎症、重置免疫系统以及胰岛移植。本综述的目的是概述单免疫疗法试验并总结经验教训，描述近期和正在进行的联合免疫疗法试验，并就旨在保留T1D患者胰岛素分泌的未来联合临床干预策略提供观点。
联合免疫疗法在改善新发病T1D患者的短期血糖控制和胰岛素分泌方面取得了喜忧参半的结果。一些研究已成功达到改善新发病T1D患者胰岛素分泌的主要终点。然而，长期改善血糖控制和恢复胰岛素自主分泌仍然难以实现。未来的干预措施应侧重于将免疫调节与减轻β细胞应激以及解决激活自身免疫的抗原形成问题相结合的策略。
