Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Department of Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Horm Res Paediatr. 2023;96(6):631-645. doi: 10.1159/000524866. Epub 2022 May 9.
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive destruction of the pancreatic beta cells, leading to a lifelong dependence on insulin. It is associated with an increased morbidity and mortality from diabetes-related complications and a significant treatment burden. However, there has been substantial progress in therapeutic strategies that can affect the course of the disease.
This review addresses advances in immunotherapy aimed at preserving residual beta-cell function in individuals with a recent onset of T1D and arresting the disease in pre-symptomatic stages. Recent and ongoing clinical trials have investigated the efficacy and safety of various immunotherapeutic strategies aimed at targeting several mechanisms of autoimmunity, which are thought to be important in disease pathogenesis, and therapies that also address beta-cell health. So far, T-cell-directed therapies that led to a favourable balance between T-effector cell depletion or modulation and preservation or expansion of regulatory T cells have shown the most success. Furthermore, regarding the timing of intervention, teplizumab was the first immunomodulatory agent to demonstrate a significant delay in disease progression in high-risk individuals before clinical onset.
As more targeted immune interventions with potentially fewer side effects are closer to the translation into clinical practice, some new challenges may need to be addressed. The use of combination approaches that include immunotherapeutic strategies targeting different aspects of the immune system and interventions that improve beta-cell health may be required, along with the use of individualized patient-tailored approaches, a move towards early intervention, and a focus on patient-reported outcome measures.
1 型糖尿病（T1D）是一种慢性自身免疫性疾病，其特征是胰腺β细胞进行性破坏，导致终身依赖胰岛素。它与糖尿病相关并发症的发病率和死亡率增加以及治疗负担显著增加有关。然而，在可以影响疾病进程的治疗策略方面已经取得了重大进展。
本文综述了旨在保留近期发生 T1D 个体的残余β细胞功能并在无症状阶段阻止疾病进展的免疫疗法进展。最近和正在进行的临床试验已经研究了各种免疫治疗策略的疗效和安全性，这些策略旨在针对自身免疫的几个机制，这些机制被认为在疾病发病机制中很重要，并且还针对β细胞健康的疗法。到目前为止，导致 T 效应细胞耗竭或调节与调节性 T 细胞的保存或扩增之间有利平衡的 T 细胞靶向疗法显示出最大的成功。此外，就干预时机而言，teplizumab 是第一种免疫调节药物，可在临床发病前在高危个体中显著延迟疾病进展。
随着具有更少副作用的更靶向免疫干预措施更接近转化为临床实践，可能需要解决一些新的挑战。可能需要使用包括针对免疫系统不同方面的免疫治疗策略的联合方法以及改善β细胞健康的干预措施，以及使用个体化的患者量身定制方法、向早期干预转变以及关注患者报告的结果衡量标准。
