年龄对 1 型糖尿病进展和严重程度的影响：对疾病机制的潜在影响。
The Effect of Age on the Progression and Severity of Type 1 Diabetes: Potential Effects on Disease Mechanisms.
机构信息
Islet Biology Exeter (IBEx), Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK.
INSERM U1016, CNRS UMR8104, Cochin Institute, Sorbonne Paris Cité; Assistance Publique Hôpitaux de Paris, Service de Diabétologie, Cochin Hospital, INSERM and Assistance Publique Hôpitaux de Paris, Paris, France.
出版信息
Curr Diab Rep. 2018 Sep 26;18(11):115. doi: 10.1007/s11892-018-1083-4.
PURPOSE OF REVIEW
To explore the impact of age on type 1 diabetes (T1D) pathogenesis.
RECENT FINDINGS
Children progress more rapidly from autoantibody positivity to T1D and have lower C-peptide levels compared to adults. In histological analysis of post-mortem pancreata, younger age of diagnosis is associated with reduced numbers of insulin containing islets and a hyper-immune CD20 infiltrate. Moreover compared to adults, children exhibit decreased immune regulatory function and increased engagement and trafficking of autoreactive CD8 T cells, and age-related differences in β cell vulnerability may also contribute to the more aggressive immune phenotype observed in children. To account for some of these differences, HLA and non-HLA genetic loci that influence multiple disease characteristics, including age of onset, are being increasingly characterized. The exception of T1D as an autoimmune disease more prevalent in children than adults results from a combination of immune, metabolic, and genetic factors. Age-related differences in T1D pathology have important implications for better tailoring of immunotherapies.
目的综述
探讨年龄对 1 型糖尿病（T1D）发病机制的影响。
最近的发现
与成年人相比，儿童从自身抗体阳性进展为 T1D 的速度更快，C 肽水平更低。在对死后胰腺的组织学分析中，诊断时的年龄越小，含胰岛素的胰岛数量就越少，CD20 浸润也越强烈。此外，与成年人相比，儿童表现出免疫调节功能下降，自身反应性 CD8 T 细胞的募集和迁移增加，β 细胞易感性的年龄相关性差异也可能导致儿童中观察到的更具侵袭性的免疫表型。为了解释其中的一些差异，HLA 和非 HLA 遗传位点正在被越来越多地描述，这些遗传位点影响多种疾病特征，包括发病年龄。T1D 作为一种在儿童中比成年人更普遍的自身免疫性疾病的例外情况，是由免疫、代谢和遗传因素共同作用的结果。T1D 病理学中的年龄相关性差异对免疫疗法的更好调整具有重要意义。
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