Population‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus.
Objective: To determine the stage of B cell development at which a systemic lupus erythematosus (SLE)–associated DNA methylation signature originates in African American (AA) and European American (EA) subjects, and to assess whether epigenetic defects in B cell development patterns could be predict...
| Publicado en: | Arthritis & Rheumatology Vol. 72; no. 2; pp. 282 - 292 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Feb2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=141451150&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 141451150 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23265191 H06R jtl: Arthritis & Rheumatology issn: 23265191 maglogo: N pubinfo: dt: Feb2020 vid: 72 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 141451150 141451150 141451150 10.1002/art.41083 141451150 ppf: 282 ppct: 10 formats: tig: atl: Population‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus. aug: au: Breitbach, Megan E. Ramaker, Ryne C. Roberts, Kevin Kimberly, Robert P. Absher, Devin affil: University of Alabama at Huntsville and HudsonAlpha Institute for Biotechnology sug: subj: Epigenomics Lupus Erythematosus, Systemic Risk Factors Cell Differentiation B Lymphocytes Genes African Americans White Persons DNA Methylation Transcription Factors Algorithms Regression Interferons ROC Curve Female Ethnic Groups Race Factors Human Female ab: Objective: To determine the stage of B cell development at which a systemic lupus erythematosus (SLE)–associated DNA methylation signature originates in African American (AA) and European American (EA) subjects, and to assess whether epigenetic defects in B cell development patterns could be predictive of SLE status in individual and mixed immune cell populations. Methods: B cells from AA patients (n = 31) and EA patients (n = 49) with or without SLE were sorted using fluorescence‐activated cell sorting into 5 B cell subsets. DNA methylation, measured at ~460,000 CpG sites, was interrogated in each subset. Enrichment analysis of transcription factor interaction at SLE‐associated methylation sites was performed. A random forests algorithm was used to identify an epigenetic signature of SLE in the B cell subsets, which was then validated in an independent cohort of AA and EA patients and healthy controls. Results: Regression analysis across all B cell stages resulted in identification of 60 CpGs that reached genome‐wide significance for SLE‐associated methylation differences (P ≤ 1.07 × 10−7). Interrogation of ethnicity‐specific CpGs associated with SLE revealed a hypomethylated pattern that was enriched for interferon (IFN)–regulated genes and binding of EBF1 in AA patients (each P < 0.001). AA patients with SLE could be distinguished from healthy controls when the predictive model developed with the transitional B cell subset was applied to other B cell subsets (mean receiver operating characteristic [ROC] area under the curve [AUC] 0.98), and when applied to CD19+ pan–B cells (mean ROC AUC 0.95) and CD4+ pan–T cells (mean ROC AUC 0.97) from the independent validation cohort. Conclusion: These results indicate that SLE‐specific methylation patterns are ethnicity dependent. A pattern of epigenetic changes near IFN‐regulated genes early in B cell development is a hallmark of SLE in AA female subjects. EBF1 binding sites are highly enriched for significant methylation changes, implying that this may be a potential regulator of SLE‐associated epigenetic changes. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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