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部分缓解和小儿 1 型糖尿病的早期阶段表现出免疫调节变化。一项初步研究。

Partial remission and early stages of pediatric type 1 diabetes display immunoregulatory changes. A pilot study.

机构信息

Immunology Section, Germans Trias i Pujol Research Institute, Badalona, Spain.

Pediatrics Section, Germans Trias i Pujol Research Institute and University Hospital, Autonomous University of Barcelona, Badalona, Spain.

出版信息

Transl Res. 2019 Aug;210:8-25. doi: 10.1016/j.trsl.2019.03.002. Epub 2019 Mar 15.

Abstract

Type 1 diabetes (T1D) is a chronic metabolic disease of unknown etiology that results from β-cell destruction. The onset of the disease, which arises after a long asymptomatic period of autoimmune attack, may be followed by a relapsing and remitting progression, a phenomenon that is most evident during the partial remission phase (PR). This stage lasts for a few months, shows minor requirements of exogenous insulin and could be explained by a recovery of immunological tolerance. This study aims to identify new biomarkers at early stages of pediatric T1D that reflect immunoregulatory changes. To that end, pediatric patients with T1D (n = 52) and age-related control subjects (n = 30) were recruited. Immune response-related molecules and lymphocyte subsets were determined starting at T1D onset and until the second year of progression. Results showed that circulating TGF-β levels decreased during PR, and that betatrophin concentration was increased in all the considered stages without differing among studied checkpoints. Moreover, an increase of regulatory T, B and NK subsets was found during T1D progression, probably reflecting an attempt to restore self-tolerance. By contrast, a reduction in monocyte levels was observed at the early stages of diabetes. The results reveal significant changes in immunological parameters during the different early stages of T1D in children, which could ultimately serve as potential biomarkers to characterize the progression of T1D.

摘要

1 型糖尿病(T1D)是一种病因不明的慢性代谢性疾病,由β细胞破坏引起。疾病的发作是在自身免疫攻击的长时间无症状期之后发生的,随后可能会出现复发和缓解进展,这种现象在部分缓解期(PR)最为明显。这个阶段持续数月,对外源胰岛素的需求较小,可以用免疫耐受的恢复来解释。本研究旨在鉴定儿科 T1D 早期反映免疫调节变化的新生物标志物。为此,招募了 52 名儿科 T1D 患者(n=52)和年龄相关的对照受试者(n=30)。从 T1D 发病开始直至进展的第二年,测定了与免疫反应相关的分子和淋巴细胞亚群。结果表明,PR 期间循环 TGF-β水平下降,而 betatrophin 浓度在所有考虑的阶段均增加,且在研究的各个检查点之间没有差异。此外,在 T1D 进展过程中发现调节性 T、B 和 NK 亚群增加,可能反映了恢复自身耐受的尝试。相比之下,在糖尿病早期观察到单核细胞水平降低。这些结果揭示了儿童 T1D 不同早期阶段免疫参数的显著变化,这些变化最终可能成为表征 T1D 进展的潜在生物标志物。

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