A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE
Methylation variabilities of inflammatory cytokines play important roles in the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren’s syndrome (pSS). With heightened focus on personalized and precise medicine, it is necessary to compare and contrast the...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/4390789 |
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| author | Xingqiang Wang Dongyun Lei Jie Ding Shuang Liu Li Tao Fan Zhang Jiangyun Peng Jian Xu |
| author_facet | Xingqiang Wang Dongyun Lei Jie Ding Shuang Liu Li Tao Fan Zhang Jiangyun Peng Jian Xu |
| author_sort | Xingqiang Wang |
| collection | DOAJ |
| description | Methylation variabilities of inflammatory cytokines play important roles in the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren’s syndrome (pSS). With heightened focus on personalized and precise medicine, it is necessary to compare and contrast the difference and similarity of cytokine methylation status between the 3 most classic autoimmune diseases (AIDs). In this study, we integrated 5 Cytokine-Chips from genome-wide DNA methylation datasets of the 3 kind of AIDs, delta-beta value was calculated for intergroup difference, and comprehensive bioinformatics analyses of cytokine genes with aberrant methylations were performed. 125 shared differential methylation variabilities (DMVs) were identified. There were 102 shared DMVs with similar methylation status; 3 hypomethylated differential methylation regions (DMRs) across the AIDs were found, and all 3 DMRs were hypomethylated. DMRs (AZU1, LTBR, and RTEL1) were likely to serve as activator in the inflammatory process. Particularly, AZU1 and LTBR with hypomethylated TSS and first exon located in the promoter regions were able to trigger inflammation signaling cascades and play critical roles in autoimmune tautology. Moreover, functional epigenetic module (FEM) algorithm showed that different inflammatory networks are involved in different AIDs; 5 hotspots were identified as biologically plausible pathways in inducing or perpetuating of inflammation which are epigenetically deregulated in AIDs. We concluded methylation variabilities among the same cytokines can greatly impact the perpetuation of inflammatory process or signal pathway of AIDs. Differentiating the cytokine methylation status will serve as valuable resource for researchers alike to gain better understanding of the epigenetic mechanisms of the three AIDs. Even more importantly, better understanding of cytokine methylation variability existing between the three classic AIDs will aid in identification of potential epigenetic biomarkers and therapeutic targets. This trial is registered with ChiCTR-INR-16010290, a clinical trial for the treatment of rheumatoid arthritis with Warming yang and Smoothening Meridians. |
| format | Article |
| id | doaj-art-ab957d9b3f6f4c97a0ef8357ba28fa7a |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-ab957d9b3f6f4c97a0ef8357ba28fa7a2025-02-03T01:23:39ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/43907894390789A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLEXingqiang Wang0Dongyun Lei1Jie Ding2Shuang Liu3Li Tao4Fan Zhang5Jiangyun Peng6Jian Xu7Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, ChinaDepartment of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, ChinaDepartment of Liver Diseases, The Third People’s Hospital of Kunming City, Kunming, Yunnan 650041, ChinaDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, ChinaDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, ChinaDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, ChinaDepartment of Rheumatology and Immunology, The No. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650021, ChinaDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, ChinaMethylation variabilities of inflammatory cytokines play important roles in the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren’s syndrome (pSS). With heightened focus on personalized and precise medicine, it is necessary to compare and contrast the difference and similarity of cytokine methylation status between the 3 most classic autoimmune diseases (AIDs). In this study, we integrated 5 Cytokine-Chips from genome-wide DNA methylation datasets of the 3 kind of AIDs, delta-beta value was calculated for intergroup difference, and comprehensive bioinformatics analyses of cytokine genes with aberrant methylations were performed. 125 shared differential methylation variabilities (DMVs) were identified. There were 102 shared DMVs with similar methylation status; 3 hypomethylated differential methylation regions (DMRs) across the AIDs were found, and all 3 DMRs were hypomethylated. DMRs (AZU1, LTBR, and RTEL1) were likely to serve as activator in the inflammatory process. Particularly, AZU1 and LTBR with hypomethylated TSS and first exon located in the promoter regions were able to trigger inflammation signaling cascades and play critical roles in autoimmune tautology. Moreover, functional epigenetic module (FEM) algorithm showed that different inflammatory networks are involved in different AIDs; 5 hotspots were identified as biologically plausible pathways in inducing or perpetuating of inflammation which are epigenetically deregulated in AIDs. We concluded methylation variabilities among the same cytokines can greatly impact the perpetuation of inflammatory process or signal pathway of AIDs. Differentiating the cytokine methylation status will serve as valuable resource for researchers alike to gain better understanding of the epigenetic mechanisms of the three AIDs. Even more importantly, better understanding of cytokine methylation variability existing between the three classic AIDs will aid in identification of potential epigenetic biomarkers and therapeutic targets. This trial is registered with ChiCTR-INR-16010290, a clinical trial for the treatment of rheumatoid arthritis with Warming yang and Smoothening Meridians.http://dx.doi.org/10.1155/2018/4390789 |
| spellingShingle | Xingqiang Wang Dongyun Lei Jie Ding Shuang Liu Li Tao Fan Zhang Jiangyun Peng Jian Xu A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE Journal of Immunology Research |
| title | A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE |
| title_full | A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE |
| title_fullStr | A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE |
| title_full_unstemmed | A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE |
| title_short | A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE |
| title_sort | dna methylated sight on autoimmune inflammation network across ra pss and sle |
| url | http://dx.doi.org/10.1155/2018/4390789 |
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