Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients
Identifieur interne : 000666 ( 2020/Analysis ); précédent : 000665; suivant : 000667Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients
Auteurs : Amr H. Sawalha [États-Unis] ; Ming Zhao [République populaire de Chine] ; Patrick Coit [États-Unis] ; Qianjin Lu [République populaire de Chine]Source :
- Clinical Immunology (Orlando, Fla.) [ 1521-6616 ] ; 2020.
Abstract
Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specifically, we provide evidence in lupus to suggest hypomethylation and overexpression of
Url:
DOI: 10.1016/j.clim.2020.108410
PubMed: 32276140
PubMed Central: 7139239
Affiliations:
- République populaire de Chine, États-Unis
- Michigan, Pennsylvanie
- Pittsburgh
- Université de Pittsburgh
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PMC:7139239Le document en format XML
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dysregulation of <italic>ACE2</italic> and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients</title><author><name sortKey="Sawalha, Amr H" sort="Sawalha, Amr H" uniqKey="Sawalha A" first="Amr H." last="Sawalha">Amr H. Sawalha</name><affiliation wicri:level="4"><nlm:aff id="af0005">Division of Rheumatology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Rheumatology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="af0010">Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="2"><nlm:aff id="af0015">Lupus Center of Excellence, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lupus Center of Excellence, University of Pittsburgh School of Medicine, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Zhao, Ming" sort="Zhao, Ming" uniqKey="Zhao M" first="Ming" last="Zhao">Ming Zhao</name><affiliation wicri:level="1"><nlm:aff id="af0020">Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan</wicri:regionArea><wicri:noRegion>Hunan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af0025">Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan</wicri:regionArea><wicri:noRegion>Hunan</wicri:noRegion></affiliation></author><author><name sortKey="Coit, Patrick" sort="Coit, Patrick" uniqKey="Coit P" first="Patrick" last="Coit">Patrick Coit</name><affiliation wicri:level="4"><nlm:aff id="af0005">Division of Rheumatology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Rheumatology, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="2"><nlm:aff id="af0030">Graduate Immunology Program, University of Michigan School of Medicine, Ann Arbor, MI, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Graduate Immunology Program, University of Michigan School of Medicine, Ann Arbor, MI</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Lu, Qianjin" sort="Lu, Qianjin" uniqKey="Lu Q" first="Qianjin" last="Lu">Qianjin Lu</name><affiliation wicri:level="1"><nlm:aff id="af0020">Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan</wicri:regionArea><wicri:noRegion>Hunan</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af0025">Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan</wicri:regionArea><wicri:noRegion>Hunan</wicri:noRegion></affiliation></author></analytic><series><title level="j">Clinical Immunology (Orlando, Fla.)</title><idno type="ISSN">1521-6616</idno><idno type="eISSN">1521-7035</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specifically, we provide evidence in lupus to suggest hypomethylation and overexpression of <italic>ACE2</italic>, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further <italic>ACE2</italic> hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the <italic>ACE2</italic> gene might be a target for prevention and therapy in COVID-19.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C. Huang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Ren, L" uniqKey="Ren L">L. Ren</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y. 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Sawalha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Katsuyama, E" uniqKey="Katsuyama E">E. Katsuyama</name></author><author><name sortKey="Suarez Fueyo, A" uniqKey="Suarez Fueyo A">A. Suarez-Fueyo</name></author><author><name sortKey="Bradley, S J" uniqKey="Bradley S">S.J. Bradley</name></author><author><name sortKey="Mizui, M" uniqKey="Mizui M">M. Mizui</name></author><author><name sortKey="Marin, A V" uniqKey="Marin A">A.V. Marin</name></author><author><name sortKey="Mulki, L" uniqKey="Mulki L">L. Mulki</name></author><author><name sortKey="Krishfield, S" uniqKey="Krishfield S">S. Krishfield</name></author><author><name sortKey="Malavasi, F" uniqKey="Malavasi F">F. Malavasi</name></author><author><name sortKey="Yoon, J" uniqKey="Yoon J">J. Yoon</name></author><author><name sortKey="Sui, S J H" uniqKey="Sui S">S.J.H. Sui</name></author><author><name sortKey="Kyttaris, V C" uniqKey="Kyttaris V">V.C. Kyttaris</name></author><author><name sortKey="Tsokos, G C" uniqKey="Tsokos G">G.C. Tsokos</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Michigan</li><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Sawalha, Amr H" sort="Sawalha, Amr H" uniqKey="Sawalha A" first="Amr H." last="Sawalha">Amr H. Sawalha</name></region><name sortKey="Coit, Patrick" sort="Coit, Patrick" uniqKey="Coit P" first="Patrick" last="Coit">Patrick Coit</name><name sortKey="Coit, Patrick" sort="Coit, Patrick" uniqKey="Coit P" first="Patrick" last="Coit">Patrick Coit</name><name sortKey="Sawalha, Amr H" sort="Sawalha, Amr H" uniqKey="Sawalha A" first="Amr H." last="Sawalha">Amr H. Sawalha</name><name sortKey="Sawalha, Amr H" sort="Sawalha, Amr H" uniqKey="Sawalha A" first="Amr H." last="Sawalha">Amr H. Sawalha</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Zhao, Ming" sort="Zhao, Ming" uniqKey="Zhao M" first="Ming" last="Zhao">Ming Zhao</name></noRegion><name sortKey="Lu, Qianjin" sort="Lu, Qianjin" uniqKey="Lu Q" first="Qianjin" last="Lu">Qianjin Lu</name><name sortKey="Lu, Qianjin" sort="Lu, Qianjin" uniqKey="Lu Q" first="Qianjin" last="Lu">Qianjin Lu</name><name sortKey="Zhao, Ming" sort="Zhao, Ming" uniqKey="Zhao M" first="Ming" last="Zhao">Ming Zhao</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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