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Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice

Differential deoxyribonucleic acid (DNA) methylation has emerged as a critical feature of systemic lupus erythematosus (SLE). Genome-wide DNA methylation studies have revealed methylation patterns characteristic of SLE—in particular, robust hypomethylation of interferon-regulated genes is a prominen...

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Autores principales: Weeding, Emma, Sawalha, Amr H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928134/
https://www.ncbi.nlm.nih.gov/pubmed/29740453
http://dx.doi.org/10.3389/fimmu.2018.00875
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author Weeding, Emma
Sawalha, Amr H.
author_facet Weeding, Emma
Sawalha, Amr H.
author_sort Weeding, Emma
collection PubMed
description Differential deoxyribonucleic acid (DNA) methylation has emerged as a critical feature of systemic lupus erythematosus (SLE). Genome-wide DNA methylation studies have revealed methylation patterns characteristic of SLE—in particular, robust hypomethylation of interferon-regulated genes is a prominent finding in all cells of the immune system studied to date. These patterns reliably distinguish individuals with SLE from healthy controls and from individuals with other autoimmune diseases. For example, hypomethylation within IFI44L is both highly sensitive and highly specific for SLE, superior to currently available biomarkers. Furthermore, methylation status of other genetic loci has been associated with clinically relevant features of SLE including disease severity and organ-specific manifestations. Finally, DNA methylation studies have provided important insights into the pathophysiology of SLE. Most recently, there is a growing body of evidence that the transcription factor enhancer of zeste homolog 2 (EZH2) plays an important role in triggering SLE disease activity via epigenetic mechanisms, and that EZH2 blockade may be a future treatment option in SLE. In this short review, we discuss the DNA methylation patterns associated with SLE, their relationship to clinically significant features of SLE, and their implications in the development of novel diagnostic and therapeutic approaches to this complex disease.
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spelling pubmed-59281342018-05-08 Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice Weeding, Emma Sawalha, Amr H. Front Immunol Immunology Differential deoxyribonucleic acid (DNA) methylation has emerged as a critical feature of systemic lupus erythematosus (SLE). Genome-wide DNA methylation studies have revealed methylation patterns characteristic of SLE—in particular, robust hypomethylation of interferon-regulated genes is a prominent finding in all cells of the immune system studied to date. These patterns reliably distinguish individuals with SLE from healthy controls and from individuals with other autoimmune diseases. For example, hypomethylation within IFI44L is both highly sensitive and highly specific for SLE, superior to currently available biomarkers. Furthermore, methylation status of other genetic loci has been associated with clinically relevant features of SLE including disease severity and organ-specific manifestations. Finally, DNA methylation studies have provided important insights into the pathophysiology of SLE. Most recently, there is a growing body of evidence that the transcription factor enhancer of zeste homolog 2 (EZH2) plays an important role in triggering SLE disease activity via epigenetic mechanisms, and that EZH2 blockade may be a future treatment option in SLE. In this short review, we discuss the DNA methylation patterns associated with SLE, their relationship to clinically significant features of SLE, and their implications in the development of novel diagnostic and therapeutic approaches to this complex disease. Frontiers Media S.A. 2018-04-24 /pmc/articles/PMC5928134/ /pubmed/29740453 http://dx.doi.org/10.3389/fimmu.2018.00875 Text en Copyright © 2018 Weeding and Sawalha. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Weeding, Emma
Sawalha, Amr H.
Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice
title Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice
title_full Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice
title_fullStr Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice
title_full_unstemmed Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice
title_short Deoxyribonucleic Acid Methylation in Systemic Lupus Erythematosus: Implications for Future Clinical Practice
title_sort deoxyribonucleic acid methylation in systemic lupus erythematosus: implications for future clinical practice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928134/
https://www.ncbi.nlm.nih.gov/pubmed/29740453
http://dx.doi.org/10.3389/fimmu.2018.00875
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