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本文引用的文献

1
Urine Proteomics and Renal Single-Cell Transcriptomics Implicate Interleukin-16 in Lupus Nephritis.尿液蛋白质组学和肾脏单细胞转录组学提示白细胞介素-16 在狼疮肾炎中的作用。
Arthritis Rheumatol. 2022 May;74(5):829-839. doi: 10.1002/art.42023. Epub 2022 Apr 16.
2
Autoimmune Regulator Gene Polymorphisms in Egyptian Systemic Lupus Erythematosus Patients: Preliminary Results.埃及系统性红斑狼疮患者自身免疫调节基因多态性:初步结果
Int J Rheumatol. 2021 Sep 28;2021:5546639. doi: 10.1155/2021/5546639. eCollection 2021.
3
The AIRE Ser196Ser synonymous variant is a risk factor for systemic lupus erythematosus.AIRE Ser196Ser 同义变体是系统性红斑狼疮的风险因素。
Cell Immunol. 2019 Dec;346:103986. doi: 10.1016/j.cellimm.2019.103986. Epub 2019 Sep 11.
4
IL-16 expression is increased in the skin and sera of patients with systemic sclerosis.白细胞介素-16 在系统性硬化症患者的皮肤和血清中表达增加。
Rheumatology (Oxford). 2020 Mar 1;59(3):519-523. doi: 10.1093/rheumatology/kez318.
5
Correlation of myomir-206 and proinflammatory cytokines (IL-16 and IL-17) in patients with rheumatoid arthritis.类风湿关节炎患者中myomir-206与促炎细胞因子(IL-16和IL-17)的相关性
Reumatologia. 2019;57(2):72-77. doi: 10.5114/reum.2019.84811. Epub 2019 Apr 29.
6
AIRE expands: new roles in immune tolerance and beyond.AIRE的扩展:免疫耐受及其他方面的新作用。
Nat Rev Immunol. 2016 Apr;16(4):247-58. doi: 10.1038/nri.2016.9. Epub 2016 Mar 14.
7
Serum proteomic analysis identifies interleukin 16 as a biomarker for clinical response during early treatment of rheumatoid arthritis.血清蛋白质组学分析确定白细胞介素16为类风湿关节炎早期治疗期间临床反应的生物标志物。
Cytokine. 2016 Feb;78:87-93. doi: 10.1016/j.cyto.2015.12.002. Epub 2015 Dec 14.
8
Association of rs2075876 polymorphism of AIRE gene with rheumatoid arthritis risk.AIRE基因rs2075876多态性与类风湿关节炎风险的关联。
Hum Immunol. 2015 Apr;76(4):281-5. doi: 10.1016/j.humimm.2015.01.026. Epub 2015 Jan 29.
9
Epigenetics in the pathogenesis of rheumatoid arthritis.类风湿关节炎发病机制中的表观遗传学。
BMC Med. 2014 Feb 26;12:35. doi: 10.1186/1741-7015-12-35.
10
Association of AIRE polymorphisms with genetic susceptibility to rheumatoid arthritis in a Chinese population.AIRE 多态性与中国人群类风湿关节炎遗传易感性的关联。
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白塞病中白细胞介素-16和自身免疫调节因子基因启动子区域甲基化状态的研究

Investigation of methylation status of interleukin-16 and autoimmune regulator gene promoter regions in Behçet's disease.

作者信息

Akpunar Melih, Yalcin Kehribar Demet, Günaydın Serkan, Koyuncu Hilal, Celik Zülfinaz Betül, Özgen Metin

机构信息

Department of Internal Medicine, Ondokuz Mayıs University Faculty of Medicine, Samsun, Türkiye.

Department of Internal Medicine, Dokuz Eylül University Faculty of Medicine, İzmir, Türkiye.

出版信息

Arch Rheumatol. 2025 Mar 17;40(1):80-86. doi: 10.46497/ArchRheumatol.2025.11022. eCollection 2025 Mar.

DOI:10.46497/ArchRheumatol.2025.11022
PMID:40264473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12010259/
Abstract

OBJECTIVES

The aim of this study was to determine the epigenetic changes in interleukin-16 (IL-16) and autoimmune regulator genes in Behçet's disease (BD) and to investigate the relationship between these changes and the disease mechanism.

PATIENTS AND METHODS

Between October 2022 and January 2023, a total of 40 patients (20 males, 20 females; mean age: 37.0±11.4 years; range, 19 to 71 years) who met the 2014 International Criteria for Behçet's Disease with no concomitant diseases and who were either newly diagnosed or under follow-up and 40 age- and sex-matched healthy hospital staff as the control group (20 males, 20 females mean age: 35.1±5.7 years; range, 29 to 45 years) with no chronic diseases or active infections were included. Peripheral blood samples were obtained from all participants, and genomic deoxyribonucleic acid (DNA) was isolated. The DNA samples were modified using a bisulfite modification kit. Subsequently, the promoter methylation profiles of and genes were determined using methylation-specific polymerase chain reaction (MSP) with primers specifically designed for methylation.

RESULTS

In both BD and control groups, methylation was detected in the promoter region of , indicating a weak expression of the gene. In contrast, while the promoter region of the gene was methylated in all control participants, it was unmethylated in all patients with BD.

CONCLUSION

This is the first study to evaluate the methylation status of both and genes in BD. Our study results suggest that the promoter region of the gene is unmethylated in BD and that gene is activated in BD and produces autoimmune regulatory proteins that eliminate autoreactive T cells, suggesting a tendency toward autoimmunity in BD. These findings also suggest that IL-16, which is involved in the pathogenesis of many rheumatic diseases, does not play a significant role in the pathogenesis of BD.

摘要

目的

本研究旨在确定白塞病(BD)中白细胞介素-16(IL-16)和自身免疫调节基因的表观遗传变化,并探讨这些变化与疾病机制之间的关系。

患者与方法

在2022年10月至2023年1月期间,共纳入40例符合2014年白塞病国际诊断标准、无合并疾病、新诊断或正在接受随访的患者(20例男性,20例女性;平均年龄:37.0±11.4岁;范围19至71岁),以及40例年龄和性别匹配、无慢性疾病或活动性感染的健康医院工作人员作为对照组(20例男性,20例女性;平均年龄:35.1±5.7岁;范围29至45岁)。从所有参与者中采集外周血样本,并分离基因组脱氧核糖核酸(DNA)。使用亚硫酸氢盐修饰试剂盒对DNA样本进行修饰。随后,使用针对甲基化专门设计的引物,通过甲基化特异性聚合酶链反应(MSP)测定IL-16和自身免疫调节基因的启动子甲基化谱。

结果

在BD组和对照组中,均在IL-16基因启动子区域检测到甲基化,表明该基因表达较弱。相比之下,虽然自身免疫调节基因启动子区域在所有对照参与者中呈甲基化状态,但在所有BD患者中均未甲基化。

结论

这是第一项评估BD中IL-16和自身免疫调节基因甲基化状态的研究。我们的研究结果表明,BD中自身免疫调节基因启动子区域未甲基化,该基因在BD中被激活并产生消除自身反应性T细胞的自身免疫调节蛋白,提示BD存在自身免疫倾向。这些发现还表明,参与多种风湿性疾病发病机制的IL-16在BD发病机制中不起重要作用。