一项前瞻性研究中对患乳糜泻儿童外周血B细胞转录组的分析。
Profiling of peripheral blood B-cell transcriptome in children who developed coeliac disease in a prospective study.
作者信息
Oras Astrid, Kallionpää Henna, Suomi Tomi, Koskinen Satu, Laiho Asta, Elo Laura L, Knip Mikael, Lahesmaa Riitta, Aints Alar, Uibo Raivo
机构信息
Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia.
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Finland.
出版信息
Heliyon. 2023 Jan 21;9(2):e13147. doi: 10.1016/j.heliyon.2023.e13147. eCollection 2023 Feb.
BACKGROUND
In coeliac disease (CoD), the role of B-cells has mainly been considered to be production of antibodies. The functional role of B-cells has not been analysed extensively in CoD.
METHODS
We conducted a study to characterize gene expression in B-cells from children developing CoD early in life using samples collected before and at the diagnosis of the disease. Blood samples were collected from children at risk at 12, 18, 24 and 36 months of age. RNA from peripheral blood CD19 cells was sequenced and differential gene expression was analysed using R package Limma.
FINDINGS
Overall, we found one gene, , modestly downregulated in all patients (logFC -0·7; q = 0·09), and several others downregulated in those diagnosed with CoD already by the age of 2 years.
INTERPRETATION
The data highlight the role of B-cells in CoD development. The role of HNRPL in suppressing enteroviral replication suggests that the predisposing factor for both CoD and enteroviral infections is the low level of expression.
FUNDING
EU FP7 grant no. 202063, EU Regional Developmental Fund and research grant PRG712, The Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research (SyMMyS) 2012-2017, grant no. 250114) and, AoF Personalized Medicine Program (grant no. 292482), AoF grants 292335, 294337, 319280, 31444, 319280, 329277, 331790) and grants from the Sigrid Jusélius Foundation (SJF).
背景
在乳糜泻（CoD）中，B细胞的作用主要被认为是产生抗体。B细胞的功能作用在CoD中尚未得到广泛分析。
方法
我们进行了一项研究，使用疾病诊断前和诊断时采集的样本，对生命早期患CoD儿童的B细胞中的基因表达进行表征。在12、18、24和36月龄时从有患病风险的儿童中采集血样。对来自外周血CD19细胞的RNA进行测序，并使用R包Limma分析差异基因表达。
研究结果
总体而言，我们发现一个基因在所有患者中均有适度下调（logFC -0·7；q = 0·09），还有其他几个基因在2岁时就被诊断为CoD的患者中下调。
解读
数据突出了B细胞在CoD发展中的作用。HNRPL在抑制肠道病毒复制中的作用表明，CoD和肠道病毒感染的易感因素是 表达水平低。
资金支持
欧盟第七框架计划资助号202063、欧盟区域发展基金和研究资助PRG712、芬兰科学院分子系统免疫与生理学研究卓越中心（SyMMyS）2012 - 2017（资助号250114），以及芬兰科学院个性化医学计划（资助号292482）、芬兰科学院资助292335、294337、319280、31444、319280、329277、331790，以及西格丽德·尤塞利乌斯基金会（SJF）的资助。
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