1. Universidade Federal da Bahia
  2. Faculdade de Medicina da Bahia
  3. Programa de Pós-Graduação em Ciências da Saúde (PPgCS)
  4. Dissertação (PPgCS)
Please use this identifier to cite or link to this item: https://repositorio.ufba.br/handle/ri/38139
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dc.creatorFarias, Lucas de Oliveira Neves de-
dc.date.accessioned2023-10-20T17:59:06Z-
dc.date.available2023-10-20T17:59:06Z-
dc.date.issued2023-08-04-
dc.identifier.urihttps://repositorio.ufba.br/handle/ri/38139-
dc.description.abstractIntroduction: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. About 30-40% of patients develop sudden and acute inflammatory episodes, the so-called leprosy reactions. Previous studies have shown a series of miRNAs associated with leprosy phenotypes, evidencing the role of this epigenetic mechanism in the pathogenesis of the disease. Objective: This study aimed to evaluate the correlation of miRNAs previously associated with leprosy with genes linked to apoptosis and autophagy in lesions of patients with leprosy, compare the expression pattern of genes in biopsies of patients with and without reactions and describe the clinical profile and epidemiological analysis of patients with leprosy treated at reference centers in the state of Bahia, HUPES-AMN and ICOM. Methods: Biopsies of 28 patients with and without leprosy reactions, with different clinical forms of leprosy were recruited. For analysis purposes, these patients were allocated according to the WHO classification as paucibacillary (PB) or multibacillary (MB), and separated into patients with or without reactions. RNA samples contained in our biorepository were used, extracted by the method using TRIzol® Reagent (Ambion®). Obtaining complementary DNA (cDNA) was performed using the commercially available High Capacity kit (ThermoFisher). The genes were chosen because they are important in cell death processes and are regulated by the miRNAs previously analyzed by the group. Gene expression by real-time qPCR method by TaqMan® was performed and the data analyzed by comparing the threshold cycle (Ct) between groups of samples. Correlation analysis between genes and miRNAs was performed using the Spearman Correlation test, using GraphPad Prism8. Differences were considered significant when the p-value was below 0.05 (p ˂ 0.05). The patients' clinical-epidemiological database was analyzed using the R program for Windows, version 4.2.3 and the data presented in tables. Results: The expression of the genes ATG12, TNFRSF10A, PARK2, BCL2, CFLAR and STX7 was evaluated by qPCR and the expression between patients without reaction (PB + MB) and patients with reaction (RR and ENH) was compared and there was no statistically significant association in this comparison. Our results showed a correlation between miRNAs and ATG12 (miR-125a-3p), TNFRSF10A (miR-146b-5p), PARK2, CFLAR and STX7 (miR-132-5p) genes. In the epidemiological analysis, we observed that the MB form is more prevalent in males and that disease forms within this spectrum are more prone to the development of reactions, as well as affecting patients with lower educational and economic levels. Conclusion: We reinforce a role for these miRNAs in the pathogenesis of leprosy, influencing mechanisms such as apoptosis and autophagy in the skin; The MB form of the disease occurs within a social context of greater social vulnerability compared to PB patients.pt_BR
dc.description.sponsorshipINCT – DT (Instituto Nacional de Ciências e Tecnologia em Doenças Tropicais)pt_BR
dc.description.sponsorshipBolsa de Estudo da FAPESBpt_BR
dc.languageporpt_BR
dc.publisherUniversidade Federal da Bahiapt_BR
dc.subjectmiRNAspt_BR
dc.subjectGenept_BR
dc.subjecthanseníasept_BR
dc.subjectATG12pt_BR
dc.subjectTNFRSF10Apt_BR
dc.subjectPARK2pt_BR
dc.subjectBCL2pt_BR
dc.subjectCFLARpt_BR
dc.subjectSTX7pt_BR
dc.subject.othermiRNAspt_BR
dc.subject.otherGenept_BR
dc.subject.otherleprosypt_BR
dc.subject.otherATG12pt_BR
dc.subject.otherTNFRSF10Apt_BR
dc.subject.otherPARK2pt_BR
dc.subject.otherBCL2pt_BR
dc.subject.otherCFLARpt_BR
dc.subject.otherSTX7pt_BR
dc.titleCaracterização do perfil clínico-epidemiológico de uma população com hanseníase na Bahia e avaliação de microRNAs (miRNAs) ligados à via dos TLRs e sua correlação com genes de morte celular em biópsias de pacientes com hanseníasept_BR
dc.title.alternativeCharacterization of the clinical-epidemiological profile of a population with leprosy in Bahia and evaluation of microRNAs (miRNAs) linked to the TLR pathway and their correlation with cell death genes in biopsies from patients with leprosy.pt_BR
dc.typeDissertaçãopt_BR
dc.publisher.programPós-Graduação em Ciências da Saúde (POS_CIENCIAS_SAUDE) pt_BR
dc.publisher.initialsUFBApt_BR
dc.publisher.countryBrasilpt_BR
dc.subject.cnpqCNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DERMATOLOGIApt_BR
dc.subject.cnpqCNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::EPIDEMIOLOGIApt_BR
dc.subject.cnpqCNPQ::CIENCIAS BIOLOGICAS::GENETICA::GENETICA MOLECULAR E DE MICROORGANISMOSpt_BR
dc.subject.cnpqCNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA CELULARpt_BR
dc.subject.cnpqCNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOGENETICApt_BR
dc.contributor.advisor1Castellucci, Léa Cristina-
dc.contributor.advisor1IDhttps://orcid.org/0000-0002-9625-2469pt_BR
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/6921235090872091pt_BR
dc.contributor.advisor2Machado, Paulo Roberto Lima-
dc.contributor.advisor2IDhttps://orcid.org/0000-0003-1894-6171pt_BR
dc.contributor.advisor2Latteshttp://lattes.cnpq.br/7641162535517337pt_BR
dc.contributor.referee1Castellucci, Léa Cristina-
dc.contributor.referee1IDhttps://orcid.org/0000-0002-9625-2469pt_BR
dc.contributor.referee1Latteshttp://lattes.cnpq.br/6921235090872091pt_BR
dc.contributor.referee2Takenami, Iukary Oliveira-
dc.contributor.referee2IDhttps://orcid.org/0000-0001-5660-7766pt_BR
dc.contributor.referee2Latteshttp://lattes.cnpq.br/5629405326727831pt_BR
dc.contributor.referee3Schriefer, Nicolaus Albert Borges-
dc.contributor.referee3IDhttps://orcid.org/0000-0002-5496-6789pt_BR
dc.contributor.referee3Latteshttp://lattes.cnpq.br/3427260889880733pt_BR
dc.creator.IDhttps://orcid.org/0009-0007-3579-361Xpt_BR
dc.creator.Latteshttp://lattes.cnpq.br/1794273267123075pt_BR
dc.description.resumoIntrodução: A hanseníase é uma doença infecciosa crônica causada pelo Mycobacterium leprae. Cerca de 30-40% dos pacientes desenvolvem episódios inflamatórios súbitos e agudos, as chamadas reações hansênicas. Estudos anteriores mostraram uma série de miRNAs associados aos fenótipos da hanseníase, evidenciando o papel desse mecanismo epigenético na patogênese da doença. Objetivo: Esse trabalho teve como objetivos avaliar a correlação de miRNAs previamente associados à hanseníase com genes ligados à apoptose e autofagia em lesões de pacientes com hanseníase, comparar o padrão de expressão dos genes em biópsias de pacientes com e sem reações e descrever o perfil clínico e epidemiológico de pacientes com hanseníase, atendidos em centros de referência do estado da Bahia, HUPES-AMN e ICOM. Métodos: Biópisas de 28 pacientes com e sem reações hansênicas, com as diversas formas clínicas da hanseníase foram recrutados. Para fins de análise, estes pacientes foram alocados de acordo com a classificação da OMS como paucibacilares (PB) ou multibacilares (MB), e separados em pacientes com ou sem reações. Foram utilizadas amostras de RNA contidas em nosso biorepositório, extraídas pelo método do utilizandoTRIzol® Reagente (Ambion®). A obtenção de DNA complementar (cDNA) foi realizada utilizando o kit comercialmente disponível High Capacity (ThermoFisher). Os genes foram escolhidos por serem importantes em processos de morte celular e serem regulados pelos miRNAs previaente analisados pelo grupo. Expressão gênica pelo método de qPCR em tempo real por TaqMan® foi realizada e os dados analisados comparando-se o ciclo limiar (Ct) entre grupos de amostras. A análise de correlação entre genes e miRNAs foi realizada por meio do teste de Correlação de Spearman, utilizando GraphPad Prism8. As diferenças foram consideradas significativas quando o valor de p ficou abaixo de 0,05 (p ˂ 0,05). O banco de dados clínico-epidemiológico dos pacientes foi analisado através do programa R para Windows, versão 4.2.3 e os dados apresentados por tabelas. Resultados: Foi avaliado por qPCR a expressão dos genes ATG12, TNFRSF10A, PARK2, BCL2, CFLAR e STX7 e comparada a expressão entre pacientes sem reação (PB + MB) e pacientes com reação, (RR e ENH) e não houve associação estatisticamente significante nesta comparação. Nossos resultados mostraram uma correlação entre os miRNAs e os genes ATG12 (miR-125a-3p), TNFRSF10A (miR-146b-5p), PARK2, CFLAR e STX7 (miR-132-5p). Na análise epidemiológica, observamos que a forma MB é mais predominante no sexo masculino e que formas doença dentro deste espectro são mais propensas ao desenvolvimento de reações, assim como atinge pacientes com menor nível educacional e econômico. Conclusão: Reforçamos um papel para esses miRNAs na patogênese da hanseníase, influenciando mecanismos como apoptose e autofagia na pele; A forma MB da doença ocorre dentro de um contexto social de maior vulnerabilidade social se comparado aos pacientes PB.pt_BR
dc.publisher.departmentFaculdade de Medicina da Bahiapt_BR
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