Akpunar Melih, Yalcin Kehribar Demet, Günaydın Serkan, Koyuncu Hilal, Celik Zülfinaz Betül, Özgen Metin
Department of Internal Medicine, Ondokuz Mayıs University Faculty of Medicine, Samsun, Türkiye.
Department of Internal Medicine, Dokuz Eylül University Faculty of Medicine, İzmir, Türkiye.
Arch Rheumatol. 2025 Mar 17;40(1):80-86. doi: 10.46497/ArchRheumatol.2025.11022. eCollection 2025 Mar.
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.
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.
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.
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.
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。
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。
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。
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。