Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | https://ri.ufs.br/handle/riufs/3581 |
Resumo: | Leprosy is a chronic infectious disease caused by Mycobacterium leprae, intracellular bacterium that causes skin lesions and neurological disorders with sensory loss. The disease constitutes a major public health problem, including Brazil. Many aspects of its immunopathogenesis are still unclear. The inability of growth in culture of bacillus impedes a greater number of experimental studies. The use of recombinant antigens is an important tool for the identification of specific proteins of M. leprae with potential for future use in immunodiagnostic tests in immunoprophylaxis and immunotherapy. The aim of this study was to evaluate the immune response to antigens of M. leprae and M. tuberculosis in protection and pathogenesis of leprosy, using a simple assay with whole blood. Patients with confirmed diagnosis of leprosy using clinical, bacteriological and histological were selected. The operational classification of patients and neurological examination to evaluate the degree of disability were performed. Patients were followed up and some of them have evolved with reactions. The controls household contacts of patients were also selected. The peripheral blood of 55 patients with leprosy, without treatment (39 paucib acillary and 16 multibacillary)and 31 controls were stimulated with antigen crude sonicate of M. leprae (MLCs), purified antigen derived from M. tuberculosis (PPD), 12 recombinant antigens of M. leprae (ML0276, ML2028, ML2055, ML2258, ML2531, ML2629, ML82F, ML2044, ML2380, ML2331, and LID1 PADL) and 2 M. tuberculosis (ID93, ID83). After 24 hours of incubation supernatants were collected and concentrations were determined cytokines IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-15, 1L-17A, IL-23, IL-27, IFN-γ, TNF-α and TGF-β, and the chemokine eotaxin, MCP-1 and MIP-1α by Luminex technique. We observed a high concentration of IFN-γ and IL-2 (response Th1) in response to antigens MLCs and PPD in patients with paucibacillary forms and controls in contacts of patients, compared to those with multibacillary forms of the disease. However, no statistically significant differences were observed when analyzing the response to such antigens in patients who subsequently developed with leprosy reactions (n=26) and did not develop leprosy reaction (n = 16) and had the beginning of treatment, degree of disability Physical 0 (n=22) in comparison with the first and second (n=33). Higher concentrations of IFN-γ were detected in patients paucibacillary PADL in response to antigen when compared with patients multibacillary. There was also increased production of MCP-1 in response to ML2531 ID93 and in patients who developed reactions. In conclusion, the production of MCP1 in response to antigens ML 2531 and ID93 can be assayed as a marker of leprosy reactions, antigen MLCs shows a behavior similar to PPD antigen and may be a marker of protective response in leprosy. The PADL antigen may be associated with induction of protective response, suggesting that PADL and MLCs are promising antigens for use in immunotherapy or immunoprophylaxis in leprosy. |
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Simon, Marise do Valehttp://lattes.cnpq.br/6248026330837543Jesus, Amélia Maria Ribeiro dehttp://lattes.cnpq.br/32121338252239802017-09-26T12:07:12Z2017-09-26T12:07:12Z2013-02-01SIMON, Marise do Vale. Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase. 2013. 145 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2013.https://ri.ufs.br/handle/riufs/3581Leprosy is a chronic infectious disease caused by Mycobacterium leprae, intracellular bacterium that causes skin lesions and neurological disorders with sensory loss. The disease constitutes a major public health problem, including Brazil. Many aspects of its immunopathogenesis are still unclear. The inability of growth in culture of bacillus impedes a greater number of experimental studies. The use of recombinant antigens is an important tool for the identification of specific proteins of M. leprae with potential for future use in immunodiagnostic tests in immunoprophylaxis and immunotherapy. The aim of this study was to evaluate the immune response to antigens of M. leprae and M. tuberculosis in protection and pathogenesis of leprosy, using a simple assay with whole blood. Patients with confirmed diagnosis of leprosy using clinical, bacteriological and histological were selected. The operational classification of patients and neurological examination to evaluate the degree of disability were performed. Patients were followed up and some of them have evolved with reactions. The controls household contacts of patients were also selected. The peripheral blood of 55 patients with leprosy, without treatment (39 paucib acillary and 16 multibacillary)and 31 controls were stimulated with antigen crude sonicate of M. leprae (MLCs), purified antigen derived from M. tuberculosis (PPD), 12 recombinant antigens of M. leprae (ML0276, ML2028, ML2055, ML2258, ML2531, ML2629, ML82F, ML2044, ML2380, ML2331, and LID1 PADL) and 2 M. tuberculosis (ID93, ID83). After 24 hours of incubation supernatants were collected and concentrations were determined cytokines IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-15, 1L-17A, IL-23, IL-27, IFN-γ, TNF-α and TGF-β, and the chemokine eotaxin, MCP-1 and MIP-1α by Luminex technique. We observed a high concentration of IFN-γ and IL-2 (response Th1) in response to antigens MLCs and PPD in patients with paucibacillary forms and controls in contacts of patients, compared to those with multibacillary forms of the disease. However, no statistically significant differences were observed when analyzing the response to such antigens in patients who subsequently developed with leprosy reactions (n=26) and did not develop leprosy reaction (n = 16) and had the beginning of treatment, degree of disability Physical 0 (n=22) in comparison with the first and second (n=33). Higher concentrations of IFN-γ were detected in patients paucibacillary PADL in response to antigen when compared with patients multibacillary. There was also increased production of MCP-1 in response to ML2531 ID93 and in patients who developed reactions. In conclusion, the production of MCP1 in response to antigens ML 2531 and ID93 can be assayed as a marker of leprosy reactions, antigen MLCs shows a behavior similar to PPD antigen and may be a marker of protective response in leprosy. The PADL antigen may be associated with induction of protective response, suggesting that PADL and MLCs are promising antigens for use in immunotherapy or immunoprophylaxis in leprosy.A hanseníase é uma doença infecciosa crônica causada pelo Mycobacterium leprae, bactéria intracelular que causa lesões cutâneas e neurológicas com perda de sensibilidade. A doença se constitue num importante problema de saúde pública, inclusive no Brasil. Muitos aspectos da sua imunopatogênese ainda não foram esclarecidos. A impossibilidade de crescimento do bacilo em cultura inviabiliza um maior número de estudos experimentais. O uso de antígenos recombinantes é uma importante ferramenta na identificação de proteínas específicas do M. leprae com potencial para utilização futura em testes imunodiagnósticos, em imunoprofilaxia e imunoterapia. O objetivo desse trabalho foi avaliar a resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e patogênese da hanseníase, utilizando um ensaio simples com sangue total. Pacientes com diagnóstico confirmado de hanseníase utilizando critérios clínicos, baciloscópico e histopatológico foram selecionados. A classificação operacional dos pacientes e o exame neurológico para avaliação do grau de incapacidade física foram realizados. Os pacientes foram acompanhados e alguns deles evoluíram com reações hansênicas. Os controles intradomiciliares contactantes dos pacientes foram também selecionados. O sangue periférico de 55 pacientes com hanseníase, sem tratamento (39 paucibacilar e 16 multibacilar) e 31 controles foram estimulados com o antígeno bruto sonicado de M. leprae (MLCS), antígeno purificado derivado de M. tuberculosis (PPD), 12 antígenos recombinantes de M. leprae (ML0276, ML2028, ML2055, ML2258, ML2531, ML2629, ML82F, ML2044, ML2380, ML2331, LID1 e PADL) e 2 de M. tuberculosis (ID93, ID83). Após 24h de incubação os sobrenadantes foram coletados e foram determinadas as concentrações das citocinas IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13 IL-15, 1L-17A, IL- 23, IL-27, IFN-γ, TNF-α e TGF-β, e das quimiocinas eotaxina, MCP-1 e MIP-1α, pela técnica de Luminex. Foi observada uma elevada concentração de IFN-γ e IL-2 (resposta Th1) em resposta aos antígenos MLCS e PPD em pacientes com as formas paucibacilares e nos controles contactantes dos doentes, quando comparados àqueles com as formas multibacilares da doença. Porém, não foi observado diferenças estatisticamente significativas quando analisada a resposta a esses mesmos antígenos em pacientes que posteriormente evoluíram com reações hansênicas (n=26) e não evoluíram com reação hansênica (n=16) e que tinham ao início do tratamento, grau de incapacidade física 0 (n=22) em comparação com 1 e 2 (n=33). Maiores concentrações de IFN-γ foram detectadas em pacientes paucibacilares em resposta ao antígeno PADL, quando comparado com os pacientes multibacilares. Houve também maior produção de MCP-1 em resposta ao ID93 e ML2531 nos pacientes que evoluíram com reações hansênicas. Em conclusão, a produção de MCP1 em resposta aos antígenos ID93 e ML 2531 pode ser testada como marcador de reações hansênicas, o antígeno MLCS apresenta um comportamento semelhante ao antígeno PPD e pode ser um marcador de resposta protetora na hanseníase. O antígeno PADL pode estar associado à indução de resposta protetora, sugerindo que MLCS e PADL são antígenos promissores para utilização em imunoterapia ou imunoprofilaxia na hanseníase.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de SergipePós-Graduação em Ciências da SaúdeUFSBRHanseníaseMycobacterium lepraeAntígenosResposta imuneLeprosyMycobacterium lepraeAntigensImmune responseCNPQ::CIENCIAS DA SAUDEResposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSTEXTMARISE_VALE_SIMON.pdf.txtMARISE_VALE_SIMON.pdf.txtExtracted texttext/plain345704https://ri.ufs.br/jspui/bitstream/riufs/3581/2/MARISE_VALE_SIMON.pdf.txtc4a1f97fdc959a6bc33347afbb9babcbMD52THUMBNAILMARISE_VALE_SIMON.pdf.jpgMARISE_VALE_SIMON.pdf.jpgGenerated Thumbnailimage/jpeg1379https://ri.ufs.br/jspui/bitstream/riufs/3581/3/MARISE_VALE_SIMON.pdf.jpg8df22eb87f1ad2f084e13aef0c996b57MD53ORIGINALMARISE_VALE_SIMON.pdfapplication/pdf3332303https://ri.ufs.br/jspui/bitstream/riufs/3581/1/MARISE_VALE_SIMON.pdf1c13f2af9264b926c59ee4e9536c234dMD51riufs/35812017-11-28 17:01:24.098oai:ufs.br:riufs/3581Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2017-11-28T20:01:24Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.por.fl_str_mv |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase |
title |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase |
spellingShingle |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase Simon, Marise do Vale Hanseníase Mycobacterium leprae Antígenos Resposta imune Leprosy Mycobacterium leprae Antigens Immune response CNPQ::CIENCIAS DA SAUDE |
title_short |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase |
title_full |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase |
title_fullStr |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase |
title_full_unstemmed |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase |
title_sort |
Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase |
author |
Simon, Marise do Vale |
author_facet |
Simon, Marise do Vale |
author_role |
author |
dc.contributor.author.fl_str_mv |
Simon, Marise do Vale |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6248026330837543 |
dc.contributor.advisor1.fl_str_mv |
Jesus, Amélia Maria Ribeiro de |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3212133825223980 |
contributor_str_mv |
Jesus, Amélia Maria Ribeiro de |
dc.subject.por.fl_str_mv |
Hanseníase Mycobacterium leprae Antígenos Resposta imune |
topic |
Hanseníase Mycobacterium leprae Antígenos Resposta imune Leprosy Mycobacterium leprae Antigens Immune response CNPQ::CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
Leprosy Mycobacterium leprae Antigens Immune response |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS DA SAUDE |
description |
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, intracellular bacterium that causes skin lesions and neurological disorders with sensory loss. The disease constitutes a major public health problem, including Brazil. Many aspects of its immunopathogenesis are still unclear. The inability of growth in culture of bacillus impedes a greater number of experimental studies. The use of recombinant antigens is an important tool for the identification of specific proteins of M. leprae with potential for future use in immunodiagnostic tests in immunoprophylaxis and immunotherapy. The aim of this study was to evaluate the immune response to antigens of M. leprae and M. tuberculosis in protection and pathogenesis of leprosy, using a simple assay with whole blood. Patients with confirmed diagnosis of leprosy using clinical, bacteriological and histological were selected. The operational classification of patients and neurological examination to evaluate the degree of disability were performed. Patients were followed up and some of them have evolved with reactions. The controls household contacts of patients were also selected. The peripheral blood of 55 patients with leprosy, without treatment (39 paucib acillary and 16 multibacillary)and 31 controls were stimulated with antigen crude sonicate of M. leprae (MLCs), purified antigen derived from M. tuberculosis (PPD), 12 recombinant antigens of M. leprae (ML0276, ML2028, ML2055, ML2258, ML2531, ML2629, ML82F, ML2044, ML2380, ML2331, and LID1 PADL) and 2 M. tuberculosis (ID93, ID83). After 24 hours of incubation supernatants were collected and concentrations were determined cytokines IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-15, 1L-17A, IL-23, IL-27, IFN-γ, TNF-α and TGF-β, and the chemokine eotaxin, MCP-1 and MIP-1α by Luminex technique. We observed a high concentration of IFN-γ and IL-2 (response Th1) in response to antigens MLCs and PPD in patients with paucibacillary forms and controls in contacts of patients, compared to those with multibacillary forms of the disease. However, no statistically significant differences were observed when analyzing the response to such antigens in patients who subsequently developed with leprosy reactions (n=26) and did not develop leprosy reaction (n = 16) and had the beginning of treatment, degree of disability Physical 0 (n=22) in comparison with the first and second (n=33). Higher concentrations of IFN-γ were detected in patients paucibacillary PADL in response to antigen when compared with patients multibacillary. There was also increased production of MCP-1 in response to ML2531 ID93 and in patients who developed reactions. In conclusion, the production of MCP1 in response to antigens ML 2531 and ID93 can be assayed as a marker of leprosy reactions, antigen MLCs shows a behavior similar to PPD antigen and may be a marker of protective response in leprosy. The PADL antigen may be associated with induction of protective response, suggesting that PADL and MLCs are promising antigens for use in immunotherapy or immunoprophylaxis in leprosy. |
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2013 |
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2017-09-26T12:07:12Z |
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SIMON, Marise do Vale. Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase. 2013. 145 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2013. |
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https://ri.ufs.br/handle/riufs/3581 |
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SIMON, Marise do Vale. Resposta imune a antígenos de M. leprae e M. tuberculosis na proteção e na patogênese da hanseníase. 2013. 145 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2013. |
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