Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa

Detalhes bibliográficos
Autor(a) principal: ALMEIDA, Cristina de Melo Cardoso
Data de Publicação: 2007
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
dARK ID: ark:/38995/0013000000p3m
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tde/1834
Resumo: Tuberculosis (TB) caused by the Mycobacterium tuberculosis is responsible for more than 2 million deaths annually in the world. Although one third of the world population carries the bacilli, only 5% of the infected people develop active disease. 80% of TB cases are concentrated among 21 countries and Brazil is one of them. Due to the flaws existent inherent to the TB diagnostic, many works try to discover TB antigens to be used on an ELISA assay to detect active TB in underdeveloped countries, endemic for other mycobacterias such as leprosy (L). Several researches are identifying bacilli proteins obtained under nutritional culture stress, in order to mimic the intracellular milieu. It has been selected the immunodominant ones as a disease marker. The objective of this work was to characterize the humoral immune response among TB patients to rMPT-51 and rGlcB using an ELISA indirect test. It was included voluntaries that were HIV negative and the ones without pregnancy, chronic disease or under immunosuppressant treatment. Serum IgM and IgG against MPT-51 and GlcB recombinant antigen from 49 patients with active tuberculosis were measured by indirect ELISA, paired by sex and age with: healthy PPD negative individuals (controls) and lepromatous leprosy patients (LL). Patients with TB (0.810±0.319) showed higher levels of IgM against rMPT-51 than both LL individuals (0.454±0.195) and control (0.448±0.162) with statistical significant, p= 0.001 and p<0.001) respectively. These test showed 96.9% specificity and 67.3% sensitivity. Conversely, tuberculosis, controls, and LL individuals showed lower of MPT-51 IgG levels, which could not be distinguished among the groups. rGlcB antigen was able to distinguished TB patients from controls for IgM levels (specificity, 95.9 % and sensitivity, 8.2% ) and IgG levels (specificity, 99% and sensitivity, 18.2%). In order to evaluate the profiles of IgM and IgG against rMPT-51 and rGlcB before and after chemotherapy, the sera from 11 patients was collected and paired according to the treatment status (before or after). IgM and IgG against MPT-51 remained with the same profile levels before and after the treatment. The levels of serum IgG against rGlcB clearly diminished after the chemotherapy (p<0.01). Our results suggest that serum IgM levels against recombinant MPT-51 could to be useful to distinguish between active TB, controls and LL individuals. In addition, after TB treatment the IgG response to rGlcB diminished suggesting that it could be used to follow up of the TB treatment
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spelling KIPNIS, Ana Paula Junqueirahttp://lattes.cnpq.br/1252262903952987ALMEIDA, Cristina de Melo Cardoso2014-07-29T15:30:42Z2008-05-092007-02-23ALMEIDA, Cristina de Melo Cardoso. HUMORAL IMMUNE RESPONSES OF TUBERCULOSIS PATIENTS IN BRAZIL INDICATE RECOGNITION OF Mycobacterium tuberculosis MPT-51 AND GLCB. 2007. 132 f. Dissertação (Mestrado em Medicina) - Universidade Federal de Goiás, Goiânia, 2007.http://repositorio.bc.ufg.br/tede/handle/tde/1834ark:/38995/0013000000p3mTuberculosis (TB) caused by the Mycobacterium tuberculosis is responsible for more than 2 million deaths annually in the world. Although one third of the world population carries the bacilli, only 5% of the infected people develop active disease. 80% of TB cases are concentrated among 21 countries and Brazil is one of them. Due to the flaws existent inherent to the TB diagnostic, many works try to discover TB antigens to be used on an ELISA assay to detect active TB in underdeveloped countries, endemic for other mycobacterias such as leprosy (L). Several researches are identifying bacilli proteins obtained under nutritional culture stress, in order to mimic the intracellular milieu. It has been selected the immunodominant ones as a disease marker. The objective of this work was to characterize the humoral immune response among TB patients to rMPT-51 and rGlcB using an ELISA indirect test. It was included voluntaries that were HIV negative and the ones without pregnancy, chronic disease or under immunosuppressant treatment. Serum IgM and IgG against MPT-51 and GlcB recombinant antigen from 49 patients with active tuberculosis were measured by indirect ELISA, paired by sex and age with: healthy PPD negative individuals (controls) and lepromatous leprosy patients (LL). Patients with TB (0.810±0.319) showed higher levels of IgM against rMPT-51 than both LL individuals (0.454±0.195) and control (0.448±0.162) with statistical significant, p= 0.001 and p<0.001) respectively. These test showed 96.9% specificity and 67.3% sensitivity. Conversely, tuberculosis, controls, and LL individuals showed lower of MPT-51 IgG levels, which could not be distinguished among the groups. rGlcB antigen was able to distinguished TB patients from controls for IgM levels (specificity, 95.9 % and sensitivity, 8.2% ) and IgG levels (specificity, 99% and sensitivity, 18.2%). In order to evaluate the profiles of IgM and IgG against rMPT-51 and rGlcB before and after chemotherapy, the sera from 11 patients was collected and paired according to the treatment status (before or after). IgM and IgG against MPT-51 remained with the same profile levels before and after the treatment. The levels of serum IgG against rGlcB clearly diminished after the chemotherapy (p<0.01). Our results suggest that serum IgM levels against recombinant MPT-51 could to be useful to distinguish between active TB, controls and LL individuals. In addition, after TB treatment the IgG response to rGlcB diminished suggesting that it could be used to follow up of the TB treatmentA tuberculose (TB) causada pelo Mycobacterium tuberculosis, resulta em mais de dois milhões de óbitos anualmente. Segundo dados da OMS cerca de 30% da população mundial está infectada com o bacilo e 5% desses infectados desenvolvem a doença ativa. O Brasil juntamente com outros 21 países albergam 80% de todos os casos de TB no mundo. Devido às falhas existentes nos diagnósticos atuais, muitos estudos tentam descobrir antígenos do Mycobacterium tuberculosis que podem ser usados no ensaio ELISA, um teste de baixo custo. Esse teste seria de grande valia na identificação da tuberculose, principalmente em países em desenvolvimento endêmicos também para outras micobactérias como M. leprae, causador da hanseníase. Várias pesquisas têm identificado componentes do bacilo, como as proteínas secretadas pelas micobactérias em cultura, sob condições de estresse nutricional, mimetizando a situação vivida pelo bacilo no meio intracelular. Dessas proteínas são selecionadas aquelas imunodominantes que podem ser usadas como marcadores da doença. O objetivo desse trabalho foi avaliar o reconhecimento de duas dessas proteínas: os antígenos recombinantes MPT-51 e GlcB do M. tuberculosis, por anticorpos séricos da classe IgM e IgG de pacientes com tuberculose ativa, pelo método imunoenzimático indireto (ELISA). Foram adotados como critério de inclusão aqueles indivíduos de qualquer grupo que fossem HIV negativos, sem doenças crônicas ou uso de medicamentos imunossupressores e mulheres não gestantes. Quarenta e nove pacientes com tuberculose ativa foram selecionados e comparados com os grupos: controles saudáveis PPD não reatores e pacientes hansenianos portadores da forma Virchoviana, pareados por sexo e idade. Os pacientes com TB (0,810±0,319) mostraram maiores concentrações de IgM anti-MPT-51 que os seus respectivos controles: pacientes com hanseníase 0,454±0,195) e controles saudáveis (0,448±0,162), com diferença estatística, p=0,001 e p<0,001 respectivamente. Os ensaios de ELISA nas dosagens de IgM e IgG anti-MPT-51 mostraram especificidade de 96,9% e 98,0% e sensibilidade 67,3% e 4,1% respectivamente. Para o antígeno GlcB, os ensaios de ELISA na dosagem de IgM e IgG mostraram especificidade de 95,9% e 99% e sensibilidade 8,2% e 18,2%. Onze pacientes com TB foram monitorados durante o tratamento, com realização de dosagens dos níveis de anticorpos IgM e IgG específicos ao rMPT-51 e rGlcB antes e após a terapia. Os níveis de anticorpos IgM e IgG anti-MPT-51 antes e após a terapia não sofreram alterações significativas. Entretanto, os níveis de IgG anti-GlcB diminuíram após a terapia (p<0,01). Nossos resultados sugerem que o rMPT-51 pode ser usado como marcador da tuberculose, quando mensuradas as concentrações de IgM específicos, pois foram capazes de discriminar pacientes TB, de controles e hansenianos. Apesar do ELISA ter demonstrado baixa sensibilidade quando o antígeno rGlcB foi utilizado, os níveis séricos dos anticorpos da classe IgG diminuíram após o tratamento da tuberculose (p<0,01) sugerindo que essa técnica poderia ser utilizada para o acompanhamento da terapêuticaMade available in DSpace on 2014-07-29T15:30:42Z (GMT). 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dc.title.por.fl_str_mv Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
dc.title.alternative.none.fl_str_mv HUMORAL IMMUNE RESPONSES OF TUBERCULOSIS PATIENTS IN BRAZIL INDICATE RECOGNITION OF Mycobacterium tuberculosis MPT-51 AND GLCB
title Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
spellingShingle Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
ALMEIDA, Cristina de Melo Cardoso
ANTÍGENO
ANTICORPO
TUBERCULOSE
ELISA
RESPOSTA IMUNE HUMORAL
MPT-51
GLCB
Tuberculose - Diagnóstico Teste imunoenzimático (ELISA) Mycobacterium tuberculosis Antígenos (GlcB) Antígenos (MPT-51) Anticorpos - Resposta humoral
ANTIGEN
ANTIBODY
TUBERCULOSIS
ELISA
HUMORAL IMMUNE RESPONSE
MPT-51
GLCB
CNPQ::CIENCIAS DA SAUDE::MEDICINA
title_short Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
title_full Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
title_fullStr Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
title_full_unstemmed Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
title_sort Reconhecimento dos Antígenos Recombinantes MPT-51 e GlcB do Mycobacterium tuberculosis por Anticorpos Séricos de Indivíduos com Tuberculose Ativa
author ALMEIDA, Cristina de Melo Cardoso
author_facet ALMEIDA, Cristina de Melo Cardoso
author_role author
dc.contributor.advisor1.fl_str_mv KIPNIS, Ana Paula Junqueira
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1252262903952987
dc.contributor.author.fl_str_mv ALMEIDA, Cristina de Melo Cardoso
contributor_str_mv KIPNIS, Ana Paula Junqueira
dc.subject.por.fl_str_mv ANTÍGENO
ANTICORPO
TUBERCULOSE
ELISA
RESPOSTA IMUNE HUMORAL
MPT-51
GLCB
Tuberculose - Diagnóstico Teste imunoenzimático (ELISA) Mycobacterium tuberculosis Antígenos (GlcB) Antígenos (MPT-51) Anticorpos - Resposta humoral
ANTIGEN
ANTIBODY
TUBERCULOSIS
ELISA
HUMORAL IMMUNE RESPONSE
MPT-51
GLCB
topic ANTÍGENO
ANTICORPO
TUBERCULOSE
ELISA
RESPOSTA IMUNE HUMORAL
MPT-51
GLCB
Tuberculose - Diagnóstico Teste imunoenzimático (ELISA) Mycobacterium tuberculosis Antígenos (GlcB) Antígenos (MPT-51) Anticorpos - Resposta humoral
ANTIGEN
ANTIBODY
TUBERCULOSIS
ELISA
HUMORAL IMMUNE RESPONSE
MPT-51
GLCB
CNPQ::CIENCIAS DA SAUDE::MEDICINA
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA
description Tuberculosis (TB) caused by the Mycobacterium tuberculosis is responsible for more than 2 million deaths annually in the world. Although one third of the world population carries the bacilli, only 5% of the infected people develop active disease. 80% of TB cases are concentrated among 21 countries and Brazil is one of them. Due to the flaws existent inherent to the TB diagnostic, many works try to discover TB antigens to be used on an ELISA assay to detect active TB in underdeveloped countries, endemic for other mycobacterias such as leprosy (L). Several researches are identifying bacilli proteins obtained under nutritional culture stress, in order to mimic the intracellular milieu. It has been selected the immunodominant ones as a disease marker. The objective of this work was to characterize the humoral immune response among TB patients to rMPT-51 and rGlcB using an ELISA indirect test. It was included voluntaries that were HIV negative and the ones without pregnancy, chronic disease or under immunosuppressant treatment. Serum IgM and IgG against MPT-51 and GlcB recombinant antigen from 49 patients with active tuberculosis were measured by indirect ELISA, paired by sex and age with: healthy PPD negative individuals (controls) and lepromatous leprosy patients (LL). Patients with TB (0.810±0.319) showed higher levels of IgM against rMPT-51 than both LL individuals (0.454±0.195) and control (0.448±0.162) with statistical significant, p= 0.001 and p<0.001) respectively. These test showed 96.9% specificity and 67.3% sensitivity. Conversely, tuberculosis, controls, and LL individuals showed lower of MPT-51 IgG levels, which could not be distinguished among the groups. rGlcB antigen was able to distinguished TB patients from controls for IgM levels (specificity, 95.9 % and sensitivity, 8.2% ) and IgG levels (specificity, 99% and sensitivity, 18.2%). In order to evaluate the profiles of IgM and IgG against rMPT-51 and rGlcB before and after chemotherapy, the sera from 11 patients was collected and paired according to the treatment status (before or after). IgM and IgG against MPT-51 remained with the same profile levels before and after the treatment. The levels of serum IgG against rGlcB clearly diminished after the chemotherapy (p<0.01). Our results suggest that serum IgM levels against recombinant MPT-51 could to be useful to distinguish between active TB, controls and LL individuals. In addition, after TB treatment the IgG response to rGlcB diminished suggesting that it could be used to follow up of the TB treatment
publishDate 2007
dc.date.issued.fl_str_mv 2007-02-23
dc.date.available.fl_str_mv 2008-05-09
dc.date.accessioned.fl_str_mv 2014-07-29T15:30:42Z
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dc.identifier.citation.fl_str_mv ALMEIDA, Cristina de Melo Cardoso. HUMORAL IMMUNE RESPONSES OF TUBERCULOSIS PATIENTS IN BRAZIL INDICATE RECOGNITION OF Mycobacterium tuberculosis MPT-51 AND GLCB. 2007. 132 f. Dissertação (Mestrado em Medicina) - Universidade Federal de Goiás, Goiânia, 2007.
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dc.identifier.dark.fl_str_mv ark:/38995/0013000000p3m
identifier_str_mv ALMEIDA, Cristina de Melo Cardoso. HUMORAL IMMUNE RESPONSES OF TUBERCULOSIS PATIENTS IN BRAZIL INDICATE RECOGNITION OF Mycobacterium tuberculosis MPT-51 AND GLCB. 2007. 132 f. Dissertação (Mestrado em Medicina) - Universidade Federal de Goiás, Goiânia, 2007.
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