Institute for Science & Technology in Medicine, Keele University, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.
Haywood Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Stoke-on-Trent, Staffordshire, ST6 7AG, UK.
Epigenomics. 2016 Feb;8(2):209-24. doi: 10.2217/epi.15.103. Epub 2015 Nov 10.
Although aberrant DNA methylation has been described in rheumatoid arthritis (RA), no studies have interrogated this epigenetic modification in early disease. Following recent investigations of T and B lymphocytes in established disease, we now characterize in these cell populations genome-wide DNA methylation in treatment-naive patients with early RA.
PATIENTS & METHODS: HumanMethylation450 BeadChips were used to examine genome-wide DNA methylation in lymphocyte populations from 23 early RA patients and 11 healthy individuals.
Approximately 2000 CpGs in each cell type were differentially methylated in early RA. Clustering analysis identified a novel methylation signature in each cell type (150 sites in T lymphocytes, 113 sites in B lymphocytes) that clustered all patients separately from controls. A subset of sites differentially methylated in early RA displayed similar changes in established disease.
Treatment-naive early RA patients display novel disease-specific DNA methylation aberrations, supporting a potential role for these changes in the development of RA.
虽然类风湿关节炎（RA）存在异常的 DNA 甲基化，但尚无研究探讨早期疾病中的这种表观遗传修饰。在对已确诊疾病中的 T 淋巴细胞和 B 淋巴细胞进行了近期研究后，我们现在对未经治疗的早期 RA 患者的这些细胞群进行了全基因组 DNA 甲基化分析。
采用 HumanMethylation450 BeadChips 检测 23 例早期 RA 患者和 11 例健康个体的淋巴细胞群中的全基因组 DNA 甲基化。
在早期 RA 中，每种细胞类型中约有 2000 个 CpG 发生甲基化差异。聚类分析在每种细胞类型中（T 淋巴细胞 150 个位点，B 淋巴细胞 113 个位点）鉴定出了一个新的甲基化特征，该特征将所有患者与对照组区分开来。早期 RA 中存在差异甲基化的一些位点在已确诊疾病中也显示出类似的变化。
未经治疗的早期 RA 患者表现出新型疾病特异性 DNA 甲基化异常，这支持这些变化在 RA 发展中的潜在作用。
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