Department of Diabetes Immunology, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, USA; Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Faculty of Life Sciences & Medicine, King's College London, London, UK.
Lancet Diabetes Endocrinol. 2019 Jan;7(1):65-74. doi: 10.1016/S2213-8587(18)30109-8. Epub 2018 Oct 24.
Precision medicine has emerged as a mantra for therapeutic approaches to complex diseases. The defining concept relies on a detailed insight into disease pathogenesis and therapeutic mechanism. Although the type 1 diabetes field has gained new insights into disease endotypes and indications of efficacy for several therapies, none of these is yet licensed, partly because of immune suppressive side-effects beyond control of islet autoimmunity. New strategies designed to regulate the immune system continue to emerge as basic science discoveries are made, including the use of antigen-based immunotherapies. A single agent or approach seems unlikely to halt disease progression in all people with or at risk of type 1 diabetes; as such, tailored methods relying on patient subgroups and knowledge of disease endotypes are gaining attention. Recent insights into disease mechanisms and emerging trial data are being translated into opportunities for tissue-specific prevention of progressive loss of β-cell function and survival. Results so far point to feasibility, safety, and tolerability of administration of islet autoantigens and peptides thereof into recipients with or at risk of type 1 diabetes. Findings from mechanistic studies suggest favourable changes in islet autoimmunity, with signs of immune regulation. Major challenges remain, including those related to dose and dosing frequency, route of administration, and use of adjuvants. However, the first steps towards tissue-specific and personalised medicine in type 1 diabetes have been made, which will guide future studies into induction of immune tolerance to intervene in the initiation and progression of islet autoimmunity and disease.
精准医学已成为治疗复杂疾病的一种方法。其定义概念依赖于对疾病发病机制和治疗机制的深入了解。尽管 1 型糖尿病领域对疾病亚型和几种疗法的疗效指标有了新的认识，但这些都尚未获得许可，部分原因是除了胰岛自身免疫之外，免疫抑制的副作用无法控制。随着基础科学发现的不断涌现，包括使用基于抗原的免疫疗法，旨在调节免疫系统的新策略继续出现。单一药物或方法似乎不太可能阻止所有 1 型糖尿病患者或有患病风险的患者的疾病进展；因此，依赖于患者亚组和疾病亚型知识的针对性方法越来越受到关注。最近对疾病机制的深入了解和新兴试验数据正在转化为针对β细胞功能进行渐进性丧失和存活的组织特异性预防的机会。到目前为止的结果表明，在有或有 1 型糖尿病风险的患者中给予胰岛自身抗原及其肽是可行的、安全的和耐受的。机制研究的结果表明，胰岛自身免疫有有利的变化，有免疫调节的迹象。仍然存在重大挑战，包括剂量和给药频率、给药途径和佐剂的使用。然而，已经朝着 1 型糖尿病的组织特异性和个体化医学迈出了第一步，这将指导未来诱导免疫耐受以干预胰岛自身免疫和疾病的启动和进展的研究。
