Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells.
Distinct DNA Methylation Patterns of Rheumatoid Arthritis Peripheral Blood and Synovial Tissue T Cells.
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类风湿关节炎外周血和滑膜组织T细胞的不同DNA甲基化模式。
DOI：
10.1002/acr2.11231
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发表时间：
2021-03
影响因子：
3.4
通讯作者：
Firestein GS
中科院分区：
文献类型：
--
作者：
Ai R;Boyle DL;Wang W;Firestein GS
为了研究聚集在类风湿关节炎(RA)滑膜中的T淋巴细胞的表观遗传学模式，我们研究了类风湿关节炎(RA)和骨关节炎(OA)患者外周血和滑膜组织中CD3+T细胞的DNA甲基化。用抗体和磁珠从RA(n=8)和OA(n=5)患者关节成形术时的血液或滑膜中提取CD3+T细胞的基因组DNA。用Illumina Infinium甲基化EPIC试剂盒测定甲基化。差异甲基化基因(DML)和差异甲基化基因(DMGs)的鉴定采用韦氏t检验。使用主成分分析、等级聚类和通径分析来确定组之间的关系。当我们比较每个疾病的外周血和滑膜组织中CD3+T细胞的DNA甲基化时，在RA和OA样本中分别发现4615和164个DML，导致832和36个DMG。主成分分析表明，T细胞的甲基化差异更大的基础是位置(血液和滑膜)，而不是疾病(类风湿关节炎和骨关节炎)。RA血液和滑膜T细胞之间的差异修饰通路显著丰富，尤其是与补体、整合素细胞表面相互作用和P53通路相关的基因。在骨性关节炎血液和滑膜T细胞之间发现的DMG数量有限，与生物学途径不符。类风湿性关节炎的DNA甲基化模式表现出与免疫途径相关的位置特异性差异，而骨性关节炎的甲基化差异有限。RA的联合特异性特征可能是由于T细胞群体的选择性聚集或差异标记的适应性免疫细胞的扩张。了解表观遗传模式可以为RA关节中聚集的T细胞类型提供线索，并确定潜在的治疗靶点。
To study epigenetic patterns in T lymphocytes that accumulate in the rheumatoid arthritis (RA) synovium, we characterized DNA methylation of CD3+ T cells in peripheral blood and synovial tissue in patients with RA and osteoarthritis (OA). Genomic DNA of CD3+ T cells was isolated from patients with RA (n = 8) and OA (n = 5) from blood or the synovium at the time of an arthroplasty using antibodies and magnetic beads. Methylation was measured by using the Illumina Infinium MethylationEPIC Kit. Differentially methylated loci (DML) and differentially methylated genes (DMGs) were identified by using Welch’s t‐test. Principal component analysis, hierarchical clustering, and pathway analysis were used to determine relationships among groups. When we compared DNA methylation of CD3+ T cells between peripheral blood and synovial tissue within each disease, 4615 and 164 DML were identified in RA and OA samples, respectively, resulting in 832 and 36 DMGs. A principal component analysis showed that methylation differences in T cells were greater on the basis of on location (blood vs synovium) rather than disease (RA vs OA). Differentially modified pathways were significantly enriched between RA blood and synovial T cells, especially in genes related to complement, integrin cell surface interactions, and the P53 pathway. The limited number of DMGs identified between OA blood and synovial T cells did not conform to biologic pathways. The patterns of DNA methylation in RA show location‐specific differences related to immune pathways, whereas methylation differences in OA are limited. The RA joint‐specific signatures could be due to selective accumulation of T‐cell populations or expansion of differentially marked adaptive immune cells. Understanding epigenetic patterns could provide clues to the types of T cells that accumulate in the RA joint and identify potential therapeutic targets.
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DOI：
10.1002/art.39952
发表时间：
2017-03
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
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
通讯作者：
Criswell LA
影响因子：
--
作者：
Nielsen, Helene Myrtue;Tost, Jorg
通讯作者：
Tost, Jorg
类风湿关节炎中关节特异性 DNA 甲基化和转录组特征识别不同的致病过程
影响因子：
16.6
作者：
Ai R;Hammaker D;Boyle DL;Morgan R;Walsh AM;Fan S;Firestein GS;Wang W
通讯作者：
Wang W
影响因子：
3.7
作者：
Glossop, John R.;Emes, Richard D.;Farrell, William E.
通讯作者：
Farrell, William E.
影响因子：
5.8
作者：
Aryee, Martin J.;Jaffe, Andrew E.;Irizarry, Rafael A.
通讯作者：
Irizarry, Rafael A.