Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFG |
dARK ID: | ark:/38995/001300000dw4c |
Texto Completo: | http://repositorio.bc.ufg.br/tede/handle/tede/6602 |
Resumo: | Leprosy is a complex dermato-neurological disease that presents multiple clinical forms and its differential diagnosis requires clinical expertise. The clinical manifestations in leprosy are defined by the type of imune response developed by the patient: cellular/Th1 or humoral/Th2 in paucibacillary/PB and multibacillary disease respectively. Multidrugtherapy (MDT) is considered efficacious however its impact on the immune responses of PB and MB leprosy patients remains unknown. Currently no single laboratory test is capable to detect all clinical forms of leprosy and laboratory tests are not available to aid the differential diagnosis. This study evaluated the impact of MDT on both cell-mediated immunity (CMI) and antibody responses by the follow up of untreated PB and MB leprosy patients evaluated at 2 time points after MDT using a panel of recombinants M. leprae proteins (rML). At diagnosis, PB patients produced interferon gamma (IFNγ), and MB patients exhibited low or absent response. Shortly after MDT, IFNγ production was observed only to LID-1 in PB and MB leprosy patients (p<0,05). Almost 2 years after MDT, IFNγ levels declined in PB and MB patients. Most untreated PB patients were seronegative to PGL-I and rML, remaining so after MDT. Most untreated MB patients were seropositive to all antigens, and IgG to rMLs declined after MDT. Reduction in antigen-specific CMI in PB and in antibody response in MB patients may help monitor MDT effectiveness but may also have a role in the risk of relapse/reinfection. This study also evaluated the usefulness of cellular test (Whole blood assay – WBA to LID-1) and serology to PGL-I and LID-1 to differential diagnosis of leprosy. Newly diagnosed and untreated PB and MB leprosy patients, patients with other dermatoses clinically suspect of leprosy and healthy endemic individuals were recruited in two geographic areas of Brazil (Goiânia and Fortaleza). Higher IFN levels to LID-1 were detected in PB leprosy patients when compared to all other study groups: MB patients (p<0.0001), other dermatoses (p=0.0008) and endemic controls (p<0.0001). In MB patients, the seroreactivity to LID-1 and PGL-I was statistically different from: PB leprosy (p<0.0001), other dermatoses (p<0.0001) and endemic controls (p<0.0001). The IFN detection by WBA-LID-1 and the serology to PGL-I and LID-1 were able to discriminate leprosy patients from patients with other dermatoses indicating their utility for the differential diagnosis of leprosy. |
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Stefani, Mariane Martins de Araújohttp://lattes.cnpq.br/5581414958714905Esquenazi, Danuza de AlmeidaSouza, Vânia Nieto Brito deAraújo Filho, João Alves deKipnis, Ana Paula JunqueiraStefani, Mariane Martins de Araújohttp://lattes.cnpq.br/8547174206385284Freitas, Aline de Araújo2016-12-16T13:48:42Z2015-09-25FREITAS, A. A. Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses. 2015. 133. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2016.http://repositorio.bc.ufg.br/tede/handle/tede/6602ark:/38995/001300000dw4cLeprosy is a complex dermato-neurological disease that presents multiple clinical forms and its differential diagnosis requires clinical expertise. The clinical manifestations in leprosy are defined by the type of imune response developed by the patient: cellular/Th1 or humoral/Th2 in paucibacillary/PB and multibacillary disease respectively. Multidrugtherapy (MDT) is considered efficacious however its impact on the immune responses of PB and MB leprosy patients remains unknown. Currently no single laboratory test is capable to detect all clinical forms of leprosy and laboratory tests are not available to aid the differential diagnosis. This study evaluated the impact of MDT on both cell-mediated immunity (CMI) and antibody responses by the follow up of untreated PB and MB leprosy patients evaluated at 2 time points after MDT using a panel of recombinants M. leprae proteins (rML). At diagnosis, PB patients produced interferon gamma (IFNγ), and MB patients exhibited low or absent response. Shortly after MDT, IFNγ production was observed only to LID-1 in PB and MB leprosy patients (p<0,05). Almost 2 years after MDT, IFNγ levels declined in PB and MB patients. Most untreated PB patients were seronegative to PGL-I and rML, remaining so after MDT. Most untreated MB patients were seropositive to all antigens, and IgG to rMLs declined after MDT. Reduction in antigen-specific CMI in PB and in antibody response in MB patients may help monitor MDT effectiveness but may also have a role in the risk of relapse/reinfection. This study also evaluated the usefulness of cellular test (Whole blood assay – WBA to LID-1) and serology to PGL-I and LID-1 to differential diagnosis of leprosy. Newly diagnosed and untreated PB and MB leprosy patients, patients with other dermatoses clinically suspect of leprosy and healthy endemic individuals were recruited in two geographic areas of Brazil (Goiânia and Fortaleza). Higher IFN levels to LID-1 were detected in PB leprosy patients when compared to all other study groups: MB patients (p<0.0001), other dermatoses (p=0.0008) and endemic controls (p<0.0001). In MB patients, the seroreactivity to LID-1 and PGL-I was statistically different from: PB leprosy (p<0.0001), other dermatoses (p<0.0001) and endemic controls (p<0.0001). The IFN detection by WBA-LID-1 and the serology to PGL-I and LID-1 were able to discriminate leprosy patients from patients with other dermatoses indicating their utility for the differential diagnosis of leprosy.A hanseníase é uma doença dermato-neurológica complexa que apresenta múltiplas formas clínicas e o diagnóstico diferencial requer expertise clínica. As manifestações clínicas da hanseníase são definidas de acordo com o tipo de resposta imune do paciente, a qual pode ser celular/Th1 na doença paucibacilar (PB) ou humoral/Th2 na doença multibacilar (MB). A multidrogaterapia (MDT) é considerada eficaz, todavia, pouco se sabe sobre seu impacto na resposta imune de pacientes com hanseníase PB e MB. Não existe um teste laboratorial único adequado para o diagnóstico de todas as formas clínicas da hanseníase e que possa contribuir para o diagnóstico diferencial. Este estudo avaliou o impacto da MDT nas respostas imune celular e humoral de pacientes PB e MB recém-diagnosticados, não tratados em dois momentos após a conclusão da MDT utilizando um painel de proteínas recombinantes do M. leprae (rMLs). Ao diagnóstico, pacientes PB produziram IFN para todas as rMLs, pacientes MB produziram baixos níveis de IFN. Cerca de 4-8 meses após o término da MDT observou-se aumento nos níveis de IFN em pacientes PB e MB (p<0,05), contudo, não houve produção de IFN cerca de 2 anos após o término da MDT. A sororeatividade de pacientes PB ao diagnóstico foi negativa para a maioria das rMLs e para o PGL-I e este perfil não foi modificado após a MDT. Ao diagnóstico pacientes MB apresentaram alta soropositividade para rMLs e PGL-I após a MDT os níveis de IgG declinaram. A redução nos níveis de IFN para LID-1 em pacientes PB e o declínio de IgG em pacientes MB podem auxiliar no monitoramento da eficácia da MDT, entretanto não se sabe qual a repercussão desta redução no risco de recidiva/reinfecção. Este estudo também avaliou a utilidade do teste de imunidade celular (ensaio de sangue total/EST para LID-1) e da sorologia para PGL-I e LID-1 no diagnóstico diferencial da hanseníase. Pacientes PB e MB recém- diagnosticados, não tratados, pacientes com outras dermatoses clinicamente semelhantes à hanseníase e indivíduos saudáveis de área endêmica (EC) foram recrutados em duas áreas endêmicas do Brasil (Goiânia e Fortaleza). Maiores níveis de IFN para LID-1 foram detectados em pacientes PB quando comparados aos outros grupos de estudo: MB (p<0,0001), outras dermatoses (p=0,0008) e EC (p<0,0001). Em pacientes MB a sororeatividade para LID-1 e PGL-I foi estatisticamente diferente quando comparada com pacientes PB (p<0,0001), pacientes com outras dermatoses (p<0,0001) e EC (p<0,0001). A detecção de IFN e a sorologia para PGL-I e LID-1 foram capazes de discriminar pacientes PB e MB de pacientes com outras dermatoses indicando a utilidade destes testes no diagnóstico diferencial da hanseníase.Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2016-12-16T09:22:11Z No. of bitstreams: 2 Tese - Aline de Araujo Freitas - 2015.pdf: 4592269 bytes, checksum: 4e3d268a1c9a9eb3594460d9effc4237 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2016-12-16T13:48:42Z (GMT) No. of bitstreams: 2 Tese - Aline de Araujo Freitas - 2015.pdf: 4592269 bytes, checksum: 4e3d268a1c9a9eb3594460d9effc4237 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2016-12-16T13:48:42Z (GMT). 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dc.title.por.fl_str_mv |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses |
dc.title.alternative.eng.fl_str_mv |
Cellular and humoral response to recombinant proteins of Mycobacterium leprae in leprosy patients after multidrugtherapy and patients with other dermatoses |
title |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses |
spellingShingle |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses Freitas, Aline de Araújo Hanseníase Multidrogaterapia Dermatoses Leprosy Multidrugtherapy Dermatoses CIENCIAS BIOLOGICAS::IMUNOLOGIA |
title_short |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses |
title_full |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses |
title_fullStr |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses |
title_full_unstemmed |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses |
title_sort |
Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses |
author |
Freitas, Aline de Araújo |
author_facet |
Freitas, Aline de Araújo |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Stefani, Mariane Martins de Araújo |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5581414958714905 |
dc.contributor.referee1.fl_str_mv |
Esquenazi, Danuza de Almeida |
dc.contributor.referee2.fl_str_mv |
Souza, Vânia Nieto Brito de |
dc.contributor.referee3.fl_str_mv |
Araújo Filho, João Alves de |
dc.contributor.referee4.fl_str_mv |
Kipnis, Ana Paula Junqueira |
dc.contributor.referee5.fl_str_mv |
Stefani, Mariane Martins de Araújo |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8547174206385284 |
dc.contributor.author.fl_str_mv |
Freitas, Aline de Araújo |
contributor_str_mv |
Stefani, Mariane Martins de Araújo Esquenazi, Danuza de Almeida Souza, Vânia Nieto Brito de Araújo Filho, João Alves de Kipnis, Ana Paula Junqueira Stefani, Mariane Martins de Araújo |
dc.subject.por.fl_str_mv |
Hanseníase Multidrogaterapia Dermatoses |
topic |
Hanseníase Multidrogaterapia Dermatoses Leprosy Multidrugtherapy Dermatoses CIENCIAS BIOLOGICAS::IMUNOLOGIA |
dc.subject.eng.fl_str_mv |
Leprosy Multidrugtherapy Dermatoses |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::IMUNOLOGIA |
description |
Leprosy is a complex dermato-neurological disease that presents multiple clinical forms and its differential diagnosis requires clinical expertise. The clinical manifestations in leprosy are defined by the type of imune response developed by the patient: cellular/Th1 or humoral/Th2 in paucibacillary/PB and multibacillary disease respectively. Multidrugtherapy (MDT) is considered efficacious however its impact on the immune responses of PB and MB leprosy patients remains unknown. Currently no single laboratory test is capable to detect all clinical forms of leprosy and laboratory tests are not available to aid the differential diagnosis. This study evaluated the impact of MDT on both cell-mediated immunity (CMI) and antibody responses by the follow up of untreated PB and MB leprosy patients evaluated at 2 time points after MDT using a panel of recombinants M. leprae proteins (rML). At diagnosis, PB patients produced interferon gamma (IFNγ), and MB patients exhibited low or absent response. Shortly after MDT, IFNγ production was observed only to LID-1 in PB and MB leprosy patients (p<0,05). Almost 2 years after MDT, IFNγ levels declined in PB and MB patients. Most untreated PB patients were seronegative to PGL-I and rML, remaining so after MDT. Most untreated MB patients were seropositive to all antigens, and IgG to rMLs declined after MDT. Reduction in antigen-specific CMI in PB and in antibody response in MB patients may help monitor MDT effectiveness but may also have a role in the risk of relapse/reinfection. This study also evaluated the usefulness of cellular test (Whole blood assay – WBA to LID-1) and serology to PGL-I and LID-1 to differential diagnosis of leprosy. Newly diagnosed and untreated PB and MB leprosy patients, patients with other dermatoses clinically suspect of leprosy and healthy endemic individuals were recruited in two geographic areas of Brazil (Goiânia and Fortaleza). Higher IFN levels to LID-1 were detected in PB leprosy patients when compared to all other study groups: MB patients (p<0.0001), other dermatoses (p=0.0008) and endemic controls (p<0.0001). In MB patients, the seroreactivity to LID-1 and PGL-I was statistically different from: PB leprosy (p<0.0001), other dermatoses (p<0.0001) and endemic controls (p<0.0001). The IFN detection by WBA-LID-1 and the serology to PGL-I and LID-1 were able to discriminate leprosy patients from patients with other dermatoses indicating their utility for the differential diagnosis of leprosy. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-09-25 |
dc.date.accessioned.fl_str_mv |
2016-12-16T13:48:42Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
FREITAS, A. A. Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses. 2015. 133. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2016. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/6602 |
dc.identifier.dark.fl_str_mv |
ark:/38995/001300000dw4c |
identifier_str_mv |
FREITAS, A. A. Resposta imune celular e humoral a proteínas recombinantes do Mycobacterium leprae em pacientes com hanseníase após a multidrogaterapia e em pacientes com outras dermatoses. 2015. 133. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2016. ark:/38995/001300000dw4c |
url |
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