Cabrera Susanne M, Chen Yi-Guang, Hagopian William A, Hessner Martin J
The Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of Children's Hospital of Wisconsin, Milwaukee, WI, USA.
Section of Endocrinology, Department of Pediatrics, The Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Diabetologia. 2016 Mar;59(3):414-25. doi: 10.1007/s00125-015-3843-x. Epub 2015 Dec 23.
Type 1 diabetes mellitus is one of the most common chronic diseases in childhood. It develops through autoimmune destruction of the pancreatic beta cells and results in lifelong dependence on exogenous insulin. The pathogenesis of type 1 diabetes involves a complex interplay of genetic and environmental factors and has historically been attributed to aberrant adaptive immunity; however, there is increasing evidence for a role of innate inflammation. Over the past decade new methodologies for the analysis of nucleic acid and protein signals have been applied to type 1 diabetes. These studies are providing a new understanding of type 1 diabetes pathogenesis and have the potential to inform the development of new biomarkers for predicting diabetes onset and monitoring therapeutic interventions. In this review we will focus on blood-based signatures in type 1 diabetes, with special attention to both direct transcriptomic analyses of whole blood and immunocyte subsets, as well as plasma/serum-induced transcriptional signatures. Attention will also be given to proteomics, microRNA assays and markers of beta cell death. We will also discuss the results of blood-based profiling in type 1 diabetes within the context of the genetic and environmental factors implicated in the natural history of autoimmune diabetes.
1型糖尿病是儿童期最常见的慢性病之一。它通过胰腺β细胞的自身免疫性破坏发展而来,导致终身依赖外源性胰岛素。1型糖尿病的发病机制涉及遗传和环境因素的复杂相互作用,历史上一直归因于异常的适应性免疫;然而,越来越多的证据表明先天性炎症也起作用。在过去十年中,用于分析核酸和蛋白质信号的新方法已应用于1型糖尿病研究。这些研究为1型糖尿病的发病机制提供了新的认识,并有可能为预测糖尿病发病和监测治疗干预的新生物标志物的开发提供信息。在这篇综述中,我们将重点关注1型糖尿病基于血液的特征,特别关注全血和免疫细胞亚群的直接转录组分析以及血浆/血清诱导的转录特征。还将关注蛋白质组学、微小RNA检测和β细胞死亡标志物。我们还将在自身免疫性糖尿病自然史中涉及的遗传和环境因素的背景下讨论1型糖尿病基于血液的分析结果。