Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase

Detalhes bibliográficos
Autor(a) principal: Cunha, Maria Wiliane do Nascimento
Data de Publicação: 2020
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: http://ri.ufs.br/jspui/handle/riufs/15723
Resumo: Leprosy is a chronic infectious disease with a slow clinical evolution, caused by the intracellular bacillus Mycobacterium leprae. This disease can be classified according to operational forms in paucibacillary and multibacillary, or according to histopathological criteria in the forms: indeterminate, tuberculoid, dimorphic and virchowian. In the clinical evolution of the disease, patients may present complications such as leprosy reactions and the occurrence of physical disability. The clinical manifestations and complications of leprosy are related to several factors such as the genetic background and immunological aspects inherent to the host. However, the exact role of cytokines in the characteristics of leprosy is still unclear. Therefore, the objective of this research was to investigate the role of cytokines in the complications and clinical forms of leprosy. 104 patients diagnosed with leprosy and their contact controls (n = 70) participated in the research. These were classified according to the clinical and operational form of the disease, as well as the occurrence of leprosy reaction and physical disability. After blood collection and serum separation, the dosage of cytokines of the profiles Th1, Th2, Treg, Th17, Th9 and Th22 produced by patients and contacts using the Luminex technique was observed. Statistical analyzes were performed using the Graphpad Prisma software and the cluster formation was performed using the R program (3.6.0). We observed that cytokines of inflammatory profile IL-12p70, IFN-y, TNF- α and IL-18 were related to the virchowian form, as well as being linked to the occurrence of leprosy and physical disability. The cytokines IL-17 and IL-22 was associated with the tuberculoid form. As for the cluster analysis, it was observed the formation of a cluster formed by the cytokines IFN-γ, TNF-α, IL-9, IL-5, IL-10 and IL18 that are involved with the main complications of leprosy. On the other hand, there was formation of the cluster composed of the cytokines IL-12p70, IL-1β, IL-23, IL-5, IL-2 and IL-17A in CC, this cluster may be related to an effective immune response against M. leprae. We conclude that cytokines of the Th1 profile (IFN-y, TNF-α e IL18) are involved with leprosy complications. In addition, we identified cytokines (TNFα, IL-18, IL-4, IL-6, IL-10 e IL-27) involved in the occurrence of leprosy complications, which can function as biomarkers for monitoring the clinical course of the disease.
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spelling Cunha, Maria Wiliane do NascimentoSantos, Márcio Bezerra2022-05-19T21:27:10Z2022-05-19T21:27:10Z2020-07-01CUNHA, Maria Wiliane do Nascimento. Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase. 2020. 60 f. Dissertação (Mestrado em Biologia Parasitária) - Universidade Federal de Sergipe, São Cristóvão, 2020.http://ri.ufs.br/jspui/handle/riufs/15723Leprosy is a chronic infectious disease with a slow clinical evolution, caused by the intracellular bacillus Mycobacterium leprae. This disease can be classified according to operational forms in paucibacillary and multibacillary, or according to histopathological criteria in the forms: indeterminate, tuberculoid, dimorphic and virchowian. In the clinical evolution of the disease, patients may present complications such as leprosy reactions and the occurrence of physical disability. The clinical manifestations and complications of leprosy are related to several factors such as the genetic background and immunological aspects inherent to the host. However, the exact role of cytokines in the characteristics of leprosy is still unclear. Therefore, the objective of this research was to investigate the role of cytokines in the complications and clinical forms of leprosy. 104 patients diagnosed with leprosy and their contact controls (n = 70) participated in the research. These were classified according to the clinical and operational form of the disease, as well as the occurrence of leprosy reaction and physical disability. After blood collection and serum separation, the dosage of cytokines of the profiles Th1, Th2, Treg, Th17, Th9 and Th22 produced by patients and contacts using the Luminex technique was observed. Statistical analyzes were performed using the Graphpad Prisma software and the cluster formation was performed using the R program (3.6.0). We observed that cytokines of inflammatory profile IL-12p70, IFN-y, TNF- α and IL-18 were related to the virchowian form, as well as being linked to the occurrence of leprosy and physical disability. The cytokines IL-17 and IL-22 was associated with the tuberculoid form. As for the cluster analysis, it was observed the formation of a cluster formed by the cytokines IFN-γ, TNF-α, IL-9, IL-5, IL-10 and IL18 that are involved with the main complications of leprosy. On the other hand, there was formation of the cluster composed of the cytokines IL-12p70, IL-1β, IL-23, IL-5, IL-2 and IL-17A in CC, this cluster may be related to an effective immune response against M. leprae. We conclude that cytokines of the Th1 profile (IFN-y, TNF-α e IL18) are involved with leprosy complications. In addition, we identified cytokines (TNFα, IL-18, IL-4, IL-6, IL-10 e IL-27) involved in the occurrence of leprosy complications, which can function as biomarkers for monitoring the clinical course of the disease.A hanseníase é uma doença infecciosa crônica e de evolução clínica lenta, causada pelo bacilo intracelular Mycobacterium leprae. Essa doença pode ser classificada de acordo com suas formas operacionais em paucibacilar e multibacilar; ou segundo critérios histopatológicos nas formas clínicas: indeterminada, tuberculóide, dimorfa e virchowiana. Na evolução clínica da doença os pacientes podem apresentar complicações como as reações hansênicas e ocorrência de incapacidade física. As manifestações clínicas e complicações da hanseníase estão relacionadas a diversos fatores como o background genético e aspectos imunológicos inerentes ao hospedeiro. Contudo, ainda não está esclarecido o papel exato das citocinas nas características da hanseníase. Diante disso, o objetivo dessa pesquisa foi investigar o papel das citocinas nas complicações e formas clínicas da hanseníase. Participaram da pesquisa 104 pacientes diagnosticados com hanseníase e seus controles contactantes (n = 70). Os pacientes foram classificados quanto à forma clínica e operacional da doença, bem como à ocorrência de reação hansênica e incapacidade física. Após coleta de sangue e separação do soro, foram dosadas citocinas dos perfis Th1, Th2, Treg, Th17, Th9 e Th22 através da técnica de Luminex. As análises estatísticas foram realizadas no software Graphpad Prisma e a formação de cluster foi realizada no programa R (3.6.0). Foi observado que citocinas do perfil inflamatório IL-12p70, IFN-y, TNF-α e IL-18, apesar de pertencer ao perfil Th1, foram associados com a forma virchowiana e com a ocorrência de reação hansênica e incapacidade física. Já as citocinas IL-17 e IL-22, também do perfil inflamatório, foram associadas às formas tuberculóide. Quanto à análise de cluster, foi observado um cluster formado pelas citocinas IFN-γ, TNF-α, IL9, IL-5, IL-10 e IL-18 que estão envolvidos com as principais complicações da hanseníase. Por outro lado, houve formação do cluster composto pelas citocinas IL12p70, IL-1β, IL-23, IL-5, IL-2 e IL-17A em CC, este cluster pode estar relacionado a uma resposta imune eficaz contra M. leprae. Os resultados desse estudo demonstram que citocinas do perfil Th1 (IFN-y, TNF-α e IL-18) estão envolvidas com as complicações da hanseníase. Ademais, identificamos citocinas (TNF-α, IL-18, IL-4, IL6, IL-10 e IL-27) envolvidas na ocorrência de complicações da hanseníase, as quais podem funcionar como biomarcadores para o monitoramento da evolução clínica da doença.Fundação de Apoio a Pesquisa e à Inovação Tecnológica do Estado de Sergipe - FAPITEC/SESão CristóvãoporHanseníaseResposta imuneCitocinasResposta imunológicaCitocinasFormas clínicasImunopatogêneseLeprosyImmune responseCytokinesClinical formsImmunopathogenesisCIENCIAS BIOLOGICAS::PARASITOLOGIAAnálise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníaseAnalysis of serum cytokin profiles and clusters formation associated with clinical forms and complications of leprosyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPós-Graduação em Biologia ParasitáriaUniversidade Federal de Sergipereponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessORIGINALMARIA_WILIANE_NASCIMENTO_CUNHA.pdfMARIA_WILIANE_NASCIMENTO_CUNHA.pdfapplication/pdf2420353https://ri.ufs.br/jspui/bitstream/riufs/15723/2/MARIA_WILIANE_NASCIMENTO_CUNHA.pdfc76b8fd63093ab454e4af4392f342754MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81475https://ri.ufs.br/jspui/bitstream/riufs/15723/1/license.txt098cbbf65c2c15e1fb2e49c5d306a44cMD51TEXTMARIA_WILIANE_NASCIMENTO_CUNHA.pdf.txtMARIA_WILIANE_NASCIMENTO_CUNHA.pdf.txtExtracted texttext/plain109466https://ri.ufs.br/jspui/bitstream/riufs/15723/3/MARIA_WILIANE_NASCIMENTO_CUNHA.pdf.txtf024f018e149ae26cb0fa2048f25a475MD53THUMBNAILMARIA_WILIANE_NASCIMENTO_CUNHA.pdf.jpgMARIA_WILIANE_NASCIMENTO_CUNHA.pdf.jpgGenerated Thumbnailimage/jpeg1202https://ri.ufs.br/jspui/bitstream/riufs/15723/4/MARIA_WILIANE_NASCIMENTO_CUNHA.pdf.jpg948822db906629bd9591e5214412f39aMD54riufs/157232022-05-19 18:27:30.724oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2022-05-19T21:27:30Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.pt_BR.fl_str_mv Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
dc.title.alternative.eng.fl_str_mv Analysis of serum cytokin profiles and clusters formation associated with clinical forms and complications of leprosy
title Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
spellingShingle Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
Cunha, Maria Wiliane do Nascimento
Hanseníase
Resposta imune
Citocinas
Resposta imunológica
Citocinas
Formas clínicas
Imunopatogênese
Leprosy
Immune response
Cytokines
Clinical forms
Immunopathogenesis
CIENCIAS BIOLOGICAS::PARASITOLOGIA
title_short Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
title_full Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
title_fullStr Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
title_full_unstemmed Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
title_sort Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase
author Cunha, Maria Wiliane do Nascimento
author_facet Cunha, Maria Wiliane do Nascimento
author_role author
dc.contributor.author.fl_str_mv Cunha, Maria Wiliane do Nascimento
dc.contributor.advisor1.fl_str_mv Santos, Márcio Bezerra
contributor_str_mv Santos, Márcio Bezerra
dc.subject.por.fl_str_mv Hanseníase
Resposta imune
Citocinas
Resposta imunológica
Citocinas
Formas clínicas
Imunopatogênese
topic Hanseníase
Resposta imune
Citocinas
Resposta imunológica
Citocinas
Formas clínicas
Imunopatogênese
Leprosy
Immune response
Cytokines
Clinical forms
Immunopathogenesis
CIENCIAS BIOLOGICAS::PARASITOLOGIA
dc.subject.eng.fl_str_mv Leprosy
Immune response
Cytokines
Clinical forms
Immunopathogenesis
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::PARASITOLOGIA
description Leprosy is a chronic infectious disease with a slow clinical evolution, caused by the intracellular bacillus Mycobacterium leprae. This disease can be classified according to operational forms in paucibacillary and multibacillary, or according to histopathological criteria in the forms: indeterminate, tuberculoid, dimorphic and virchowian. In the clinical evolution of the disease, patients may present complications such as leprosy reactions and the occurrence of physical disability. The clinical manifestations and complications of leprosy are related to several factors such as the genetic background and immunological aspects inherent to the host. However, the exact role of cytokines in the characteristics of leprosy is still unclear. Therefore, the objective of this research was to investigate the role of cytokines in the complications and clinical forms of leprosy. 104 patients diagnosed with leprosy and their contact controls (n = 70) participated in the research. These were classified according to the clinical and operational form of the disease, as well as the occurrence of leprosy reaction and physical disability. After blood collection and serum separation, the dosage of cytokines of the profiles Th1, Th2, Treg, Th17, Th9 and Th22 produced by patients and contacts using the Luminex technique was observed. Statistical analyzes were performed using the Graphpad Prisma software and the cluster formation was performed using the R program (3.6.0). We observed that cytokines of inflammatory profile IL-12p70, IFN-y, TNF- α and IL-18 were related to the virchowian form, as well as being linked to the occurrence of leprosy and physical disability. The cytokines IL-17 and IL-22 was associated with the tuberculoid form. As for the cluster analysis, it was observed the formation of a cluster formed by the cytokines IFN-γ, TNF-α, IL-9, IL-5, IL-10 and IL18 that are involved with the main complications of leprosy. On the other hand, there was formation of the cluster composed of the cytokines IL-12p70, IL-1β, IL-23, IL-5, IL-2 and IL-17A in CC, this cluster may be related to an effective immune response against M. leprae. We conclude that cytokines of the Th1 profile (IFN-y, TNF-α e IL18) are involved with leprosy complications. In addition, we identified cytokines (TNFα, IL-18, IL-4, IL-6, IL-10 e IL-27) involved in the occurrence of leprosy complications, which can function as biomarkers for monitoring the clinical course of the disease.
publishDate 2020
dc.date.issued.fl_str_mv 2020-07-01
dc.date.accessioned.fl_str_mv 2022-05-19T21:27:10Z
dc.date.available.fl_str_mv 2022-05-19T21:27:10Z
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dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv CUNHA, Maria Wiliane do Nascimento. Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase. 2020. 60 f. Dissertação (Mestrado em Biologia Parasitária) - Universidade Federal de Sergipe, São Cristóvão, 2020.
dc.identifier.uri.fl_str_mv http://ri.ufs.br/jspui/handle/riufs/15723
identifier_str_mv CUNHA, Maria Wiliane do Nascimento. Análise dos perfis séricos de citocinas e formação de clusters associados com as formas e complicações clínicas da hanseníase. 2020. 60 f. Dissertação (Mestrado em Biologia Parasitária) - Universidade Federal de Sergipe, São Cristóvão, 2020.
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