Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.
Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.
复制标题
DOI：
10.1002/art.39952
复制
发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Criswell LA
中科院分区：
文献类型：
--
作者：
Rhead B;Holingue C;Cole M;Shao X;Quach HL;Quach D;Shah K;Sinclair E;Graf J;Link T;Harrison R;Rahmani E;Halperin E;Wang W;Firestein GS;Barcellos LF;Criswell LA
旨在确定类风湿性关节炎 (RA) 患者滑膜来源的成纤维细胞样滑膜细胞 (FLS) 中差异甲基化的 CpG 在 RA 外周血 (PB) 样本中是否也存在差异甲基化。在本研究中，使用 Illumina HumanMmethylation450 BeadChips 测量了 63 名 RA 患者和 31 名未受影响对照受试者的 PB 样本中的 371 个全基因组 DNA 甲基化谱，特别是 CD14+ 单核细胞、CD19+ B 细胞、CD4+ 记忆 T 细胞和 CD4+ 初始 T 细胞的细胞亚群。与对照 PB 相比，在 5,532 个高甲基化 FLS 候选 CpG 中，来自 RA PB 的 CD4+ 初始 T 细胞中有 1,056 个高度甲基化。在基于 RA 全基因组关联研究的单核苷酸多态性对第二组 CpG 候选物进行分析时，在 CD4+ 记忆 T 细胞中发现了 1 个显着高甲基化的 CpG，在 CD4+ 初始 T 细胞中发现了 18 个显着的 CpG（6 个低甲基化，12 个高甲基化）。基于高甲基化 FLS 候选者的预测评分与 RA 病例状态的关联曲线下面积为 0.73，这优于 RA 与 HLA-DRB1 共享表位风险等位基因以及经过验证的 RA 遗传风险评分的关联。来自 PB 的 FLS 代表性 DNA 甲基化特征可能被证明是 RA 风险或疾病状态的有价值的生物标志物。
To determine whether differentially methylated CpGs in synovium‐derived fibroblast‐like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples. For this study, 371 genome‐wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells. Of 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single‐nucleotide polymorphisms from a genome‐wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA–DRB1 shared epitope risk allele and with a validated RA genetic risk score. FLS‐representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status.