Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou str, 10676, Athens, Greece.
Department of Endocrinology, Diabetes and Metabolic Diseases, Evangelismos General Hospital, 45-47 Ipsilantou str, 10676, Athens, Greece.
Rev Endocr Metab Disord. 2021 Dec;22(4):859-876. doi: 10.1007/s11154-021-09642-4. Epub 2021 Mar 17.
Type 1 Diabetes Mellitus (T1DM) is characterized by progressive autoimmune-mediated destruction of the pancreatic beta-cells leading to insulin deficiency and hyperglycemia. It is associated with significant treatment burden and necessitates life-long insulin therapy. The role of immunotherapy in the prevention and management of T1DM is an evolving area of interest which has the potential to alter the natural history of this disease.In this review, we give insight into recent clinical trials related to the use of immunotherapeutic approaches for T1DM, such as proinflammatory cytokine inhibition, cell-depletion and cell-therapy approaches, autoantigen-specific treatments and stem cell therapies. We highlight the timing of intervention, aspects of therapy including adverse effects and the emergence of a novel lymphocyte crucial in T1DM autoimmunity. We also discuss the role of cardiac autoimmunity and its link to excess CVD risk in T1DM.We conclude that significant advances have been made in development of immunotherapeutic targets and agents for the treatment and prevention of T1DM. These immune-based therapies promise preservation of beta-cells and decreasing insulin dependency. In their current state, immunotherapeutic approaches cannot yet halt the progression from a preclinical state to overt T1DM nor can they replace standard insulin therapy in existing T1DM. It remains to be seen whether immunotherapy will ultimately play a key role in the prevention of progression to overt T1DM and whether it may find a place in our therapeutic armamentarium to improve clinical outcomes and quality of life in established T1DM.
1 型糖尿病(T1DM)的特征是进行性自身免疫介导的胰岛β细胞破坏,导致胰岛素缺乏和高血糖。它与显著的治疗负担有关,需要终身胰岛素治疗。免疫疗法在 T1DM 的预防和管理中的作用是一个不断发展的研究领域,有可能改变这种疾病的自然病程。
在这篇综述中,我们深入探讨了最近与 T1DM 免疫治疗方法相关的临床试验,如促炎细胞因子抑制、细胞耗竭和细胞治疗方法、自身抗原特异性治疗和干细胞治疗。我们强调了干预的时间、治疗的各个方面,包括不良反应和在 T1DM 自身免疫中起关键作用的新型淋巴细胞的出现。我们还讨论了心脏自身免疫及其与 T1DM 中 CVD 风险增加的关系。
我们的结论是,在开发用于治疗和预防 T1DM 的免疫治疗靶点和药物方面取得了重大进展。这些基于免疫的疗法有望保护β细胞并减少对胰岛素的依赖。在目前的状态下,免疫治疗方法还不能阻止从临床前状态向显性 T1DM 的进展,也不能替代现有的 T1DM 中的标准胰岛素治疗。免疫疗法是否最终将在预防显性 T1DM 进展中发挥关键作用,以及它是否可能在我们的治疗武器库中找到一席之地,以改善已确诊的 T1DM 的临床结果和生活质量,仍有待观察。