Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjögren's syndrome.
Genome-wide DNA methylation patterns in naive CD4+ T cells from patients with primary Sjögren's syndrome.
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DOI：
10.1002/art.38264
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发表时间：
2014-03
影响因子：
13.3
通讯作者：
Sawalha, Amr H.
中科院分区：
文献类型：
--
作者：
Altorok, Nezam;Coit, Patrick;Hughes, Travis;Koelsch, Kristi A.;Stone, Donald U.;Rasmussen, Astrid;Radfar, Lida;Scofield, R. Hal;Sivils, Kathy L.;Farris, A. Darise;Sawalha, Amr H.
原发性Sjögren综合征（pSS）是一种病因不明的全身自身免疫性疾病。我们对表观遗传失调在pSS发病机制中的作用知之甚少。我们对11名pSS患者的naïve CD4+ T细胞进行了全基因组DNA甲基化研究，并与年龄、性别和种族匹配的健康对照进行了比较。使用Illumina Infinium HumanMethylation450 BeadChip阵列定量胞嘧啶甲基化，并使用亚硫酸盐测序进行验证。与健康对照相比，我们在pSS患者的naïve CD4+ T细胞中鉴定出553个低甲基化和200个高甲基化的CpG位点，代表311个低甲基化和115个高甲基化的基因区域。pSS中的低甲基化基因包括LTA，编码淋巴蛋白α。其他相关基因如CD247、TNFRSF25、PTPRC、GSTM1和PDCD1也被低甲基化。干扰素信号通路以STAT1、IFI44L、USP18和IFITM1的低甲基化为代表。编码溶质载体蛋白成员的一组基因被差异甲基化。此外，转录因子RUNX1在患者中被高甲基化，提示可能与淋巴瘤易感性有关。低甲基化基因的基因本体（GO）分析表明，参与淋巴细胞活化和免疫反应的基因富集。高甲基化基因的GO术语包括抗原加工和递呈。这是首次在pSS中进行表观基因组范围的DNA甲基化研究。我们的数据强调了DNA甲基化在pSS中的作用，并确定了pSS中naïve CD4+ T细胞中几种基因和途径中与疾病相关的DNA甲基化变化，这些基因和途径可能参与该疾病的发病机制。
Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease with incompletely understood etiology. Very little is known about the role of epigenetic dysregulation in the pathogenesis of pSS. We performed a genome-wide DNA methylation study in naïve CD4+ T cells in eleven pSS patients compared to age-, sex-, and ethnicity-matched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array and validated using bisulfite sequencing. We identified 553 hypomethylated and 200 hypermethylated CpG sites in naïve CD4+ T cells from pSS patients compared to healthy matched controls, representing 311 hypomethylated and 115 hypermethylated gene regions. Hypomethylated genes in pSS include LTA, coding for Lymphotoxin α. Other relevant genes such as CD247, TNFRSF25, PTPRC, GSTM1 and PDCD1 were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18 and IFITM1. A group of genes encoding for members of the solute carrier proteins were differentially methylated. In addition, the transcription factor RUNX1 was hypermethylated in patients, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation. This is the first epigenome-wide DNA methylation study in pSS. Our data highlight a role for DNA methylation in pSS and identify disease-associated DNA methylation changes in several genes and pathways in naïve CD4+ T cells in pSS that may be involved in the pathogenesis of this disease.
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影响因子：
4.9
作者：
Gatumu, Margaret K.;Skarstein, Kathrine;Papandile, Adrian;Browning, Jeffrey L.;Fava, Roy A.;Bolstad, Anne Isine
通讯作者：
Bolstad, Anne Isine
影响因子：
12.8
作者：
Coit P;Jeffries M;Altorok N;Dozmorov MG;Koelsch KA;Wren JD;Merrill JT;McCune WJ;Sawalha AH
通讯作者：
Sawalha AH
影响因子：
20.3
作者：
Kundu, M;Compton, S;Liu, PP
通讯作者：
Liu, PP
影响因子：
12.8
作者：
Mavragani, Clio P.;Crow, Mary K.
通讯作者：
Crow, Mary K.
影响因子：
20.3
作者：
Clark, Mary C.;Pang, Mabel;Baum, Linda G.
通讯作者：
Baum, Linda G.