DNA methylation patterns in juvenile systemic sclerosis and localized scleroderma.
DNA methylation patterns in juvenile systemic sclerosis and localized scleroderma.
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DOI：
10.1016/j.clim.2021.108756
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Sawalha AH
中科院分区：
文献类型：
--
作者：
Coit P;Schollaert KL;Mirizio EM;Torok KS;Sawalha AH
硬皮病是一组病因不明的慢性纤维化免疫介导的疾病。儿童期发病的硬皮病，系统性硬化症或局限性硬皮病的表观遗传变化的特点，以前没有进行。本研究的目的是评估与匹配的健康对照相比，青少年系统性硬化症（jSSc）和青少年局限性硬皮病（jLS）之间的DNA甲基化差异和相似性。使用MethylationEPIC阵列评估外周血单核细胞样品中的全基因组DNA甲基化变化，然后进行生物信息学分析和有限的功能评估。与健康对照组相比，我们在jSSc和jLS中分别鉴定了总共105个和144个差异甲基化位点。大多数差异甲基化位点和基因的代表是独特的jSSc或jLS表明在这两种疾病不同的潜在表观遗传模式。在共有的差异甲基化基因中，FGFR 2中CpG位点的甲基化水平可以高准确度区分LS和健康PBMC。经典途径分析显示，炎症途径富含jSSc中去甲基化的基因，包括STAT 3、NF-kB和IL-15途径。相比之下，HIPPO信号通路在jLS中富集。我们的数据还表明NOTCH 3在jSSc和jLS中的潜在作用，并揭示了两种疾病中每种疾病所特有的一些转录因子。总之，我们的数据揭示了对jSSc和jLS的重要见解，并提出了LS的潜在新的表观遗传诊断生物标志物。
Scleroderma refers to a group of chronic fibrotic immune-mediated diseases of unknown etiology. Characterizing epigenetic changes in childhood-onset scleroderma, systemic sclerosis or localized scleroderma, has not been previously performed. The aim of this study was to assess DNA methylation differences and similarities between juvenile systemic sclerosis (jSSc) and juvenile localized scleroderma (jLS) compared to matched healthy controls. Genome-wide DNA methylation changes in peripheral blood mononuclear cell samples were assessed using the MethylationEPIC array followed by bioinformatic analysis and limited functional assessment. We identified a total of 105 and 144 differentially methylated sites compared to healthy controls in jSSc and jLS, respectively. The majority of differentially methylated sites and genes represented were unique to either jSSc or jLS suggesting a different underlying epigenetic pattern in both diseases. Among shared differentially methylated genes, methylation levels in a CpG site in FGFR2 can distinguish between LS and healthy PBMCs with a high accuracy. Canonical pathway analysis revealed that inflammatory pathways were enriched in genes deferentially methylated in jSSc, including STAT3, NF-kB, and IL-15 pathways. In contrast, the HIPPO signaling pathway was enriched in jLS. Our data also suggest a potential role for NOTCH3 in both jSSc and jLS, and revealed a number of transcription factors unique to each for of the two diseases. In summary, our data revealed important insights into jSSc and jLS and suggest a potentially novel epigenetic diagnostic biomarker for LS.
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影响因子：
13.8
作者：
Kelsey, Christina E.;Torok, Kathryn S.
通讯作者：
Torok, Kathryn S.
局部的硬皮病皮肤严重程度指数和医师全球疾病活动评估：旨在发展局部硬皮病预后指标的工作。
DOI：
10.3899/jrheum.081284
发表时间：
2009-12
期刊：
The Journal of rheumatology
影响因子：
--
作者：
Arkachaisri T;Vilaiyuk S;Li S;O'Neil KM;Pope E;Higgins GC;Punaro M;Rabinovich EC;Rosenkranz M;Kietz DA;Rosen P;Spalding SJ;Hennon TR;Torok KS;Cassidy E;Medsger TA Jr;Localized Scleroderma Clinical and Ultrasound Study Group
通讯作者：
Localized Scleroderma Clinical and Ultrasound Study Group
影响因子：
5.5
作者：
Arkachaisri, Thaschawee;Vilaiyuk, Soamarat;Medsger, Thomas A., Jr.
通讯作者：
Medsger, Thomas A., Jr.
影响因子：
5.5
作者：
Martini, G.;Vittadello, F.;Zulian, F.
通讯作者：
Zulian, F.
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG