Gene expression patterns associated with multidrug therapy in multibacillary leprosy

Detalhes bibliográficos
Autor(a) principal: Ferreira, Helen
Data de Publicação: 2022
Outros Autores: Leal-Calvo, Thyago, Mendes, Mayara Abud, Avanzi, Charlotte, Busso, Philippe, Benjak, Andrej, Sales, Anna Maria, Ferreira, Cássio Porto, Berrêdo-Pinho, Márcia de, Cole, Stewart Thomas, Sarno, Euzenir Nunes, Moraes, Milton Ozório, Pinheiro, Roberta Olmo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/56381
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
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spelling Ferreira, HelenLeal-Calvo, ThyagoMendes, Mayara AbudAvanzi, CharlotteBusso, PhilippeBenjak, AndrejSales, Anna MariaFerreira, Cássio PortoBerrêdo-Pinho, Márcia deCole, Stewart ThomasSarno, Euzenir NunesMoraes, Milton OzórioPinheiro, Roberta Olmo2023-01-08T13:43:33Z2023-01-08T13:43:33Z2022FERREIRA, Helen et al. Gene expression patterns associated with multidrug therapy in multibacillary leprosy. Frontiers in Cellular and Infection Microbiology, v. 12, 917282, p. 1-10, July 2022.2235-2988https://www.arca.fiocruz.br/handle/icict/5638110.3389/fcimb.2022.917282engFrontiers MediaHanseníase multibacilarPoliquimioterapiaMetabolismo lipídicoCarga bacilarAssinatura genéticaMultibacillary leprosyMultidrug therapyLipid metabolismBacillary loadGene signatureGene expression patterns associated with multidrug therapy in multibacillary leprosyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland / Institut Pasteur, Paris, France.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56381/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALHelenFerreira_MiltonOzorio_etal_IOC_2022.pdfHelenFerreira_MiltonOzorio_etal_IOC_2022.pdfapplication/pdf2347902https://www.arca.fiocruz.br/bitstream/icict/56381/2/HelenFerreira_MiltonOzorio_etal_IOC_2022.pdf299fd912163ecdb81e74b2a0d20f79b2MD52icict/563812023-09-04 11:10:34.527oai:www.arca.fiocruz.br:icict/56381Q0VTU8ODTyBOw4NPIEVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUwoKQW8gYWNlaXRhciBvcyBURVJNT1MgZSBDT05EScOHw5VFUyBkZXN0YSBDRVNTw4NPLCBvIEFVVE9SIGUvb3UgVElUVUxBUiBkZSBkaXJlaXRvcwphdXRvcmFpcyBzb2JyZSBhIE9CUkEgZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvOgoKKDEpIENFREUgZSBUUkFOU0ZFUkUsIHRvdGFsIGUgZ3JhdHVpdGFtZW50ZSwgw6AgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaLCBlbQpjYXLDoXRlciBwZXJtYW5lbnRlLCBpcnJldm9nw6F2ZWwgZSBOw4NPIEVYQ0xVU0lWTywgdG9kb3Mgb3MgZGlyZWl0b3MgcGF0cmltb25pYWlzIE7Dg08KQ09NRVJDSUFJUyBkZSB1dGlsaXphw6fDo28gZGEgT0JSQSBhcnTDrXN0aWNhIGUvb3UgY2llbnTDrWZpY2EgaW5kaWNhZGEgYWNpbWEsIGluY2x1c2l2ZSBvcyBkaXJlaXRvcwpkZSB2b3ogZSBpbWFnZW0gdmluY3VsYWRvcyDDoCBPQlJBLCBkdXJhbnRlIHRvZG8gbyBwcmF6byBkZSBkdXJhw6fDo28gZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCBlbQpxdWFscXVlciBpZGlvbWEgZSBlbSB0b2RvcyBvcyBwYcOtc2VzOwoKKDIpIEFDRUlUQSBxdWUgYSBjZXNzw6NvIHRvdGFsIG7Do28gZXhjbHVzaXZhLCBwZXJtYW5lbnRlIGUgaXJyZXZvZ8OhdmVsIGRvcyBkaXJlaXRvcyBhdXRvcmFpcwpwYXRyaW1vbmlhaXMgbsOjbyBjb21lcmNpYWlzIGRlIHV0aWxpemHDp8OjbyBkZSBxdWUgdHJhdGEgZXN0ZSBkb2N1bWVudG8gaW5jbHVpLCBleGVtcGxpZmljYXRpdmFtZW50ZSwKb3MgZGlyZWl0b3MgZGUgZGlzcG9uaWJpbGl6YcOnw6NvIGUgY29tdW5pY2HDp8OjbyBww7pibGljYSBkYSBPQlJBLCBlbSBxdWFscXVlciBtZWlvIG91IHZlw61jdWxvLAppbmNsdXNpdmUgZW0gUmVwb3NpdMOzcmlvcyBEaWdpdGFpcywgYmVtIGNvbW8gb3MgZGlyZWl0b3MgZGUgcmVwcm9kdcOnw6NvLCBleGliacOnw6NvLCBleGVjdcOnw6NvLApkZWNsYW1hw6fDo28sIHJlY2l0YcOnw6NvLCBleHBvc2nDp8OjbywgYXJxdWl2YW1lbnRvLCBpbmNsdXPDo28gZW0gYmFuY28gZGUgZGFkb3MsIHByZXNlcnZhw6fDo28sIGRpZnVzw6NvLApkaXN0cmlidWnDp8OjbywgZGl2dWxnYcOnw6NvLCBlbXByw6lzdGltbywgdHJhZHXDp8OjbywgZHVibGFnZW0sIGxlZ2VuZGFnZW0sIGluY2x1c8OjbyBlbSBub3ZhcyBvYnJhcyBvdQpjb2xldMOibmVhcywgcmV1dGlsaXphw6fDo28sIGVkacOnw6NvLCBwcm9kdcOnw6NvIGRlIG1hdGVyaWFsIGRpZMOhdGljbyBlIGN1cnNvcyBvdSBxdWFscXVlciBmb3JtYSBkZQp1dGlsaXphw6fDo28gbsOjbyBjb21lcmNpYWw7CgooMykgUkVDT05IRUNFIHF1ZSBhIGNlc3PDo28gYXF1aSBlc3BlY2lmaWNhZGEgY29uY2VkZSDDoCBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPCkNSVVogbyBkaXJlaXRvIGRlIGF1dG9yaXphciBxdWFscXVlciBwZXNzb2Eg4oCTIGbDrXNpY2Egb3UganVyw61kaWNhLCBww7pibGljYSBvdSBwcml2YWRhLCBuYWNpb25hbCBvdQplc3RyYW5nZWlyYSDigJMgYSBhY2Vzc2FyIGUgdXRpbGl6YXIgYW1wbGFtZW50ZSBhIE9CUkEsIHNlbSBleGNsdXNpdmlkYWRlLCBwYXJhIHF1YWlzcXVlcgpmaW5hbGlkYWRlcyBuw6NvIGNvbWVyY2lhaXM7CgooNCkgREVDTEFSQSBxdWUgYSBvYnJhIMOpIGNyaWHDp8OjbyBvcmlnaW5hbCBlIHF1ZSDDqSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGFxdWkgY2VkaWRvcyBlIGF1dG9yaXphZG9zLApyZXNwb25zYWJpbGl6YW5kby1zZSBpbnRlZ3JhbG1lbnRlIHBlbG8gY29udGXDumRvIGUgb3V0cm9zIGVsZW1lbnRvcyBxdWUgZmF6ZW0gcGFydGUgZGEgT0JSQSwKaW5jbHVzaXZlIG9zIGRpcmVpdG9zIGRlIHZveiBlIGltYWdlbSB2aW5jdWxhZG9zIMOgIE9CUkEsIG9icmlnYW5kby1zZSBhIGluZGVuaXphciB0ZXJjZWlyb3MgcG9yCmRhbm9zLCBiZW0gY29tbyBpbmRlbml6YXIgZSByZXNzYXJjaXIgYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVogZGUKZXZlbnR1YWlzIGRlc3Blc2FzIHF1ZSB2aWVyZW0gYSBzdXBvcnRhciwgZW0gcmF6w6NvIGRlIHF1YWxxdWVyIG9mZW5zYSBhIGRpcmVpdG9zIGF1dG9yYWlzIG91CmRpcmVpdG9zIGRlIHZveiBvdSBpbWFnZW0sIHByaW5jaXBhbG1lbnRlIG5vIHF1ZSBkaXogcmVzcGVpdG8gYSBwbMOhZ2lvIGUgdmlvbGHDp8O1ZXMgZGUgZGlyZWl0b3M7CgooNSkgQUZJUk1BIHF1ZSBjb25oZWNlIGEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTwpPU1dBTERPIENSVVogZSBhcyBkaXJldHJpemVzIHBhcmEgbyBmdW5jaW9uYW1lbnRvIGRvIHJlcG9zaXTDs3JpbyBpbnN0aXR1Y2lvbmFsIEFSQ0EuCgpBIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIHJlc2VydmEKZXhjbHVzaXZhbWVudGUgYW8gQVVUT1Igb3MgZGlyZWl0b3MgbW9yYWlzIGUgb3MgdXNvcyBjb21lcmNpYWlzIHNvYnJlIGFzIG9icmFzIGRlIHN1YSBhdXRvcmlhCmUvb3UgdGl0dWxhcmlkYWRlLCBzZW5kbyBvcyB0ZXJjZWlyb3MgdXN1w6FyaW9zIHJlc3BvbnPDoXZlaXMgcGVsYSBhdHJpYnVpw6fDo28gZGUgYXV0b3JpYSBlIG1hbnV0ZW7Dp8OjbwpkYSBpbnRlZ3JpZGFkZSBkYSBPQlJBIGVtIHF1YWxxdWVyIHV0aWxpemHDp8Ojby4KCkEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVoKcmVzcGVpdGEgb3MgY29udHJhdG9zIGUgYWNvcmRvcyBwcmVleGlzdGVudGVzIGRvcyBBdXRvcmVzIGNvbSB0ZXJjZWlyb3MsIGNhYmVuZG8gYW9zIEF1dG9yZXMKaW5mb3JtYXIgw6AgSW5zdGl0dWnDp8OjbyBhcyBjb25kacOnw7VlcyBlIG91dHJhcyByZXN0cmnDp8O1ZXMgaW1wb3N0YXMgcG9yIGVzdGVzIGluc3RydW1lbnRvcy4KRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:10:34Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title Gene expression patterns associated with multidrug therapy in multibacillary leprosy
spellingShingle Gene expression patterns associated with multidrug therapy in multibacillary leprosy
Ferreira, Helen
Hanseníase multibacilar
Poliquimioterapia
Metabolismo lipídico
Carga bacilar
Assinatura genética
Multibacillary leprosy
Multidrug therapy
Lipid metabolism
Bacillary load
Gene signature
title_short Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_full Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_fullStr Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_full_unstemmed Gene expression patterns associated with multidrug therapy in multibacillary leprosy
title_sort Gene expression patterns associated with multidrug therapy in multibacillary leprosy
author Ferreira, Helen
author_facet Ferreira, Helen
Leal-Calvo, Thyago
Mendes, Mayara Abud
Avanzi, Charlotte
Busso, Philippe
Benjak, Andrej
Sales, Anna Maria
Ferreira, Cássio Porto
Berrêdo-Pinho, Márcia de
Cole, Stewart Thomas
Sarno, Euzenir Nunes
Moraes, Milton Ozório
Pinheiro, Roberta Olmo
author_role author
author2 Leal-Calvo, Thyago
Mendes, Mayara Abud
Avanzi, Charlotte
Busso, Philippe
Benjak, Andrej
Sales, Anna Maria
Ferreira, Cássio Porto
Berrêdo-Pinho, Márcia de
Cole, Stewart Thomas
Sarno, Euzenir Nunes
Moraes, Milton Ozório
Pinheiro, Roberta Olmo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ferreira, Helen
Leal-Calvo, Thyago
Mendes, Mayara Abud
Avanzi, Charlotte
Busso, Philippe
Benjak, Andrej
Sales, Anna Maria
Ferreira, Cássio Porto
Berrêdo-Pinho, Márcia de
Cole, Stewart Thomas
Sarno, Euzenir Nunes
Moraes, Milton Ozório
Pinheiro, Roberta Olmo
dc.subject.other.en_US.fl_str_mv Hanseníase multibacilar
Poliquimioterapia
Metabolismo lipídico
Carga bacilar
Assinatura genética
topic Hanseníase multibacilar
Poliquimioterapia
Metabolismo lipídico
Carga bacilar
Assinatura genética
Multibacillary leprosy
Multidrug therapy
Lipid metabolism
Bacillary load
Gene signature
dc.subject.en.en_US.fl_str_mv Multibacillary leprosy
Multidrug therapy
Lipid metabolism
Bacillary load
Gene signature
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ, Brasil.
publishDate 2022
dc.date.issued.fl_str_mv 2022
dc.date.accessioned.fl_str_mv 2023-01-08T13:43:33Z
dc.date.available.fl_str_mv 2023-01-08T13:43:33Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv FERREIRA, Helen et al. Gene expression patterns associated with multidrug therapy in multibacillary leprosy. Frontiers in Cellular and Infection Microbiology, v. 12, 917282, p. 1-10, July 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/56381
dc.identifier.issn.en_US.fl_str_mv 2235-2988
dc.identifier.doi.none.fl_str_mv 10.3389/fcimb.2022.917282
identifier_str_mv FERREIRA, Helen et al. Gene expression patterns associated with multidrug therapy in multibacillary leprosy. Frontiers in Cellular and Infection Microbiology, v. 12, 917282, p. 1-10, July 2022.
2235-2988
10.3389/fcimb.2022.917282
url https://www.arca.fiocruz.br/handle/icict/56381
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/56381/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/56381/2/HelenFerreira_MiltonOzorio_etal_IOC_2022.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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