Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease

Abstract Objectives Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease manifesting as chronic inflammation and tissue fibrosis. Since the role of DNA methylation in the pathogenesis of IgG4-RD is still unclear, we conduct this study to investigate epigenet...

Full description

Bibliographic Details
Main Authors: Xunyao Wu, Anqi Wang, Mu Wang, Yu Peng, Yingying Chen, Jieqiong Li, Zheng Liu, Hui Lu, Jiaxin Zhou, Linyi Peng, Yan Zhao, Xiaofeng Zeng, Yunyun Fei, Wen Zhang
Format: Article
Language:English
Published: BMC 2023-01-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13075-022-02978-5
_version_ 1797958539964055552
author Xunyao Wu
Anqi Wang
Mu Wang
Yu Peng
Yingying Chen
Jieqiong Li
Zheng Liu
Hui Lu
Jiaxin Zhou
Linyi Peng
Yan Zhao
Xiaofeng Zeng
Yunyun Fei
Wen Zhang
author_facet Xunyao Wu
Anqi Wang
Mu Wang
Yu Peng
Yingying Chen
Jieqiong Li
Zheng Liu
Hui Lu
Jiaxin Zhou
Linyi Peng
Yan Zhao
Xiaofeng Zeng
Yunyun Fei
Wen Zhang
author_sort Xunyao Wu
collection DOAJ
description Abstract Objectives Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease manifesting as chronic inflammation and tissue fibrosis. Since the role of DNA methylation in the pathogenesis of IgG4-RD is still unclear, we conduct this study to investigate epigenetic modifications in IgG4-RD. Methods A genome-wide DNA methylation study was conducted with B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients and matched controls by using the Illumina HumanMethylation 850K BeadChip. We further performed pyrosequencing and immunohistochemistry assays to validate the methylation status of some targets of interest. Results We identified differentially methylated CpG sites including 44 hypomethylated and 166 hypermethylated differentially methylated probes (DMPs) in B cells and 260 hypomethylated and 112 hypermethylated DMPs in CD4+ T cells from 10 IgG4-RD patients compared with 10 healthy controls. We also identified 36945 hypomethylated and 78380 hypermethylated DMPs in salivary gland tissues of 4 IgG4-RD patients compared with 4 controls. DPM2 (cg21181453), IQCK (cg10266221), and ABCC13 (cg05699681, cg04985582) were hypermethylated and MBP (cg18455083) was hypomethylated in B cells, CD4+ T cells, and salivary gland tissues of IgG4-RD patients. We also observed the hypomethylated HLA-DQB2 in CD4+ T cells from IgG4-RD patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DMPs in salivary gland tissues of IgG4-RD patients revealed enrichment of pathways involved in the regulation of immune cell responses and fibrosis. Conclusion This is the first DNA methylation study in peripheral B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients. Our findings highlighted the role of epigenetic modification of DNA methylation and identified several genes and pathways possibly involved in IgG4-RD pathogenesis.
first_indexed 2024-04-11T00:20:28Z
format Article
id doaj.art-210f434b12d54f97a06ad7cb2d0303db
institution Directory Open Access Journal
issn 1478-6362
language English
last_indexed 2024-04-11T00:20:28Z
publishDate 2023-01-01
publisher BMC
record_format Article
series Arthritis Research & Therapy
spelling doaj.art-210f434b12d54f97a06ad7cb2d0303db2023-01-08T12:17:32ZengBMCArthritis Research & Therapy1478-63622023-01-0125111110.1186/s13075-022-02978-5Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related diseaseXunyao Wu0Anqi Wang1Mu Wang2Yu Peng3Yingying Chen4Jieqiong Li5Zheng Liu6Hui Lu7Jiaxin Zhou8Linyi Peng9Yan Zhao10Xiaofeng Zeng11Yunyun Fei12Wen Zhang13Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Stomatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeAbstract Objectives Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease manifesting as chronic inflammation and tissue fibrosis. Since the role of DNA methylation in the pathogenesis of IgG4-RD is still unclear, we conduct this study to investigate epigenetic modifications in IgG4-RD. Methods A genome-wide DNA methylation study was conducted with B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients and matched controls by using the Illumina HumanMethylation 850K BeadChip. We further performed pyrosequencing and immunohistochemistry assays to validate the methylation status of some targets of interest. Results We identified differentially methylated CpG sites including 44 hypomethylated and 166 hypermethylated differentially methylated probes (DMPs) in B cells and 260 hypomethylated and 112 hypermethylated DMPs in CD4+ T cells from 10 IgG4-RD patients compared with 10 healthy controls. We also identified 36945 hypomethylated and 78380 hypermethylated DMPs in salivary gland tissues of 4 IgG4-RD patients compared with 4 controls. DPM2 (cg21181453), IQCK (cg10266221), and ABCC13 (cg05699681, cg04985582) were hypermethylated and MBP (cg18455083) was hypomethylated in B cells, CD4+ T cells, and salivary gland tissues of IgG4-RD patients. We also observed the hypomethylated HLA-DQB2 in CD4+ T cells from IgG4-RD patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DMPs in salivary gland tissues of IgG4-RD patients revealed enrichment of pathways involved in the regulation of immune cell responses and fibrosis. Conclusion This is the first DNA methylation study in peripheral B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients. Our findings highlighted the role of epigenetic modification of DNA methylation and identified several genes and pathways possibly involved in IgG4-RD pathogenesis.https://doi.org/10.1186/s13075-022-02978-5IgG4-RDDNA methylationB cellsCD4+ T cellsSalivary gland tissues
spellingShingle Xunyao Wu
Anqi Wang
Mu Wang
Yu Peng
Yingying Chen
Jieqiong Li
Zheng Liu
Hui Lu
Jiaxin Zhou
Linyi Peng
Yan Zhao
Xiaofeng Zeng
Yunyun Fei
Wen Zhang
Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease
Arthritis Research & Therapy
IgG4-RD
DNA methylation
B cells
CD4+ T cells
Salivary gland tissues
title Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease
title_full Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease
title_fullStr Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease
title_full_unstemmed Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease
title_short Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease
title_sort differential cpg dna methylation of peripheral b cells cd4 t cells and salivary gland tissues in igg4 related disease
topic IgG4-RD
DNA methylation
B cells
CD4+ T cells
Salivary gland tissues
url https://doi.org/10.1186/s13075-022-02978-5
work_keys_str_mv AT xunyaowu differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT anqiwang differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT muwang differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT yupeng differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT yingyingchen differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT jieqiongli differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT zhengliu differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT huilu differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT jiaxinzhou differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT linyipeng differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT yanzhao differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT xiaofengzeng differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT yunyunfei differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease
AT wenzhang differentialcpgdnamethylationofperipheralbcellscd4tcellsandsalivaryglandtissuesinigg4relateddisease