New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1371/journal.pone.0209599 http://hdl.handle.net/1843/56648 https://orcid.org/0000-0002-5569-4893 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-6804-4320 |
Resumo: | Visceral leishmaniasis (VL) still represents a serious public health problem in Brazil due to the inefficiency of the control measures currently employed, that included early diagnosis and treatment of human cases, vector control, euthanasia of infected dogs and, recently approved in Brazil, treatment with Milteforam drug. Effective clinical management depend largely on early and unequivocal diagnosis, however, cross-reactivity have also been described in serological tests, especially when it refers to individuals from areas where Chagas’ disease is also present. Thus, to discover new antigens to improve the current serological tests for VL diagnosis is urgently needed. Here, we performed an immunogenomic screen strategy to identify conserved linear B-cell epitopes in the predicted L. infantum proteome using the following criteria: i) proteins expressed in the stages found in the vertebrate host, amastigote stage, and secreted/excreted, to guarantee greater exposure to the immune system; ii) divergent from proteins present in other infectious disease pathogens with incidence in endemic areas for VL, as T. cruzi; iii) highly antigenic to humans with different genetic backgrounds, independently of the clinical stage of the disease; iv) stable and adaptable to quality-control tests to guarantee reproducibility; v) using statistical analysis to determine a suitable sample size to evaluate accuracy of diagnostic tests established by receiver operating characteristic strategy. We selected six predicted linear B-cell epitopes from three proteins of L. infantum parasite. The results demonstrated that a mixture of peptides (Mix IV: peptides 3+6) were able to identify VL cases and simultaneously able to discriminate infections caused by T. cruzi parasite with high accuracy (100.00%) and perfect agreement (Kappa index = 1.000) with direct methods performed by laboratories in Brazil. The results also demonstrated that peptide-6, Mix III (peptides 2+6) and I (peptides 2+3+6) are potential antigens able to used in VL diagnosis, represented by high accuracy (Ac = 99.52%, 99.52% and 98.56%, respectively). This study represents an interesting strategy for discovery new antigens applied to serologic diagnosis which will contribute to the improvement of the diagnosis of VL and, consequently, may help in the prevention, control and treatment of the disease in endemic areas of Brazil. |
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2023-07-18T20:36:04Z2023-07-18T20:36:04Z2018-12-201312https://doi.org/10.1371/journal.pone.02095991932-6203http://hdl.handle.net/1843/56648https://orcid.org/0000-0002-5569-4893https://orcid.org/0000-0002-6681-9014https://orcid.org/0000-0002-6804-4320Visceral leishmaniasis (VL) still represents a serious public health problem in Brazil due to the inefficiency of the control measures currently employed, that included early diagnosis and treatment of human cases, vector control, euthanasia of infected dogs and, recently approved in Brazil, treatment with Milteforam drug. Effective clinical management depend largely on early and unequivocal diagnosis, however, cross-reactivity have also been described in serological tests, especially when it refers to individuals from areas where Chagas’ disease is also present. Thus, to discover new antigens to improve the current serological tests for VL diagnosis is urgently needed. Here, we performed an immunogenomic screen strategy to identify conserved linear B-cell epitopes in the predicted L. infantum proteome using the following criteria: i) proteins expressed in the stages found in the vertebrate host, amastigote stage, and secreted/excreted, to guarantee greater exposure to the immune system; ii) divergent from proteins present in other infectious disease pathogens with incidence in endemic areas for VL, as T. cruzi; iii) highly antigenic to humans with different genetic backgrounds, independently of the clinical stage of the disease; iv) stable and adaptable to quality-control tests to guarantee reproducibility; v) using statistical analysis to determine a suitable sample size to evaluate accuracy of diagnostic tests established by receiver operating characteristic strategy. We selected six predicted linear B-cell epitopes from three proteins of L. infantum parasite. The results demonstrated that a mixture of peptides (Mix IV: peptides 3+6) were able to identify VL cases and simultaneously able to discriminate infections caused by T. cruzi parasite with high accuracy (100.00%) and perfect agreement (Kappa index = 1.000) with direct methods performed by laboratories in Brazil. The results also demonstrated that peptide-6, Mix III (peptides 2+6) and I (peptides 2+3+6) are potential antigens able to used in VL diagnosis, represented by high accuracy (Ac = 99.52%, 99.52% and 98.56%, respectively). This study represents an interesting strategy for discovery new antigens applied to serologic diagnosis which will contribute to the improvement of the diagnosis of VL and, consequently, may help in the prevention, control and treatment of the disease in endemic areas of Brazil.A leishmaniose visceral (LV) ainda representa um grave problema de saúde pública no Brasil devido à ineficiência das medidas de controle atualmente empregadas, que incluíam diagnóstico precoce e tratamento de casos humanos, controle de vetores, eutanásia de cães infectados e, recentemente aprovado no Brasil, tratamento com o medicamento Milteforam. O manejo clínico eficaz depende em grande parte do diagnóstico precoce e inequívoco, no entanto, reações cruzadas também têm sido descritas em testes sorológicos, principalmente quando se trata de indivíduos provenientes de áreas onde a doença de Chagas também está presente. Assim, a descoberta de novos antígenos para aprimorar os testes sorológicos atuais para o diagnóstico de LV é uma necessidade urgente. Aqui, realizamos uma estratégia de triagem imunogenômica para identificar epítopos de células B lineares conservados no pro teoma previsto de L. infantum usando os seguintes critérios: i) proteínas expressas nos estágios encontrados no hospedeiro vertebrado, estágio amastigota e secretada/excretada , para garantir maior exposição do sistema imunológico; ii) divergente de proteínas presentes em outros patógenos de doenças infecciosas com incidência em áreas endêmicas para LV, como T. cruzi; iii) altamente antigênica para humanos com diferentes backgrounds genéticos, independentemente do estágio clínico da doença; iv) estável e adaptável a testes de controle de qualidade para garantir a reprodutibilidade; v) usar análise estatística para determinar um tamanho de amostra adequado para avaliar a precisão dos testes de diagnóstico estabelecidos pela estratégia de característica operacional do receptor. Selecionamos seis epítopos de células B lineares previstos de três proteínas do parasita L. infantum. Os resultados demonstraram que uma mistura de peptídeos (Mix IV: peptídeos 3+6) foi capaz de identificar casos de LV e simultaneamente discriminar infecções causadas pelo parasita T. cruzi com alta precisão (100,00%) e concordância perfeita (índice Kappa = 1.000 ) com métodos diretos realizados por laboratórios no Brasil. Os resultados também demonstraram que o peptídeo-6, Mix III (peptídeos 2+6) e I (peptídeos 2+3+6) são potenciais antígenos aptos a serem utilizados no diagnóstico de LV, representados pela alta acurácia (Ac = 99,52%, 99,52% e 98,56%, respectivamente). Este estudo representa uma interessante estratégia de descoberta de novos antígenos aplicados ao diagnóstico sorológico que contribuirão para o aprimoramento do diagnóstico da LV e, consequentemente, poderão auxiliar na prevenção, controle e tratamento da doença em áreas endêmicas do Brasil.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorOutra AgênciaengUniversidade Federal de Minas GeraisUFMGBrasilCOLTEC - COLEGIO TECNICOPlos OneLeishmaniose visceralAntígenosEpitopos de linfócito BLeishmania infantumProteínasPeptídeosTestes sorológicosVisceral leishmaniasisAntigensImmunogenomic screenB-cell epitopesLeishmania infantumProteinsPeptidesSerologic diagnosisNew antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screeningNovos antígenos para o diagnóstico sorológico de leishmaniose visceral humana identificada por triagem imunogenômicainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209599Ana Maria Ravena Severino CarvalhoTiago Antônio de Oliveira MendesEduardo Antônio Ferraz CoelhoMariana Costa DuarteDaniel Menezes Souzaapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56648/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALNew antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening.pdfNew antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening.pdfapplication/pdf17390233https://repositorio.ufmg.br/bitstream/1843/56648/2/New%20antigens%20for%20the%20serological%20diagnosis%20of%20human%20visceral%20leishmaniasis%20identified%20by%20immunogenomic%20screening.pdfe73644dd3ecc807ba22f68f3d5d8042eMD521843/566482023-07-18 17:36:04.252oai:repositorio.ufmg.br:1843/56648TElDRU7vv71BIERFIERJU1RSSUJVSe+/ve+/vU8gTu+/vU8tRVhDTFVTSVZBIERPIFJFUE9TSVTvv71SSU8gSU5TVElUVUNJT05BTCBEQSBVRk1HCiAKCkNvbSBhIGFwcmVzZW50Ye+/ve+/vW8gZGVzdGEgbGljZW7vv71hLCB2b2Pvv70gKG8gYXV0b3IgKGVzKSBvdSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGRlIGF1dG9yKSBjb25jZWRlIGFvIFJlcG9zaXTvv71yaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIChSSS1VRk1HKSBvIGRpcmVpdG8gbu+/vW8gZXhjbHVzaXZvIGUgaXJyZXZvZ++/vXZlbCBkZSByZXByb2R1emlyIGUvb3UgZGlzdHJpYnVpciBhIHN1YSBwdWJsaWNh77+977+9byAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0cu+/vW5pY28gZSBlbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mg77+9dWRpbyBvdSB277+9ZGVvLgoKVm9j77+9IGRlY2xhcmEgcXVlIGNvbmhlY2UgYSBwb2zvv710aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRvIHNldSBkb2N1bWVudG8gZSBxdWUgY29uaGVjZSBlIGFjZWl0YSBhcyBEaXJldHJpemVzIGRvIFJJLVVGTUcuCgpWb2Pvv70gY29uY29yZGEgcXVlIG8gUmVwb3NpdO+/vXJpbyBJbnN0aXR1Y2lvbmFsIGRhIFVGTUcgcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250Ze+/vWRvLCB0cmFuc3BvciBhIHN1YSBwdWJsaWNh77+977+9byBwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHvv73vv71vLgoKVm9j77+9IHRhbWLvv71tIGNvbmNvcmRhIHF1ZSBvIFJlcG9zaXTvv71yaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIHBvZGUgbWFudGVyIG1haXMgZGUgdW1hIGPvv71waWEgZGUgc3VhIHB1YmxpY2Hvv73vv71vIHBhcmEgZmlucyBkZSBzZWd1cmFu77+9YSwgYmFjay11cCBlIHByZXNlcnZh77+977+9by4KClZvY++/vSBkZWNsYXJhIHF1ZSBhIHN1YSBwdWJsaWNh77+977+9byDvv70gb3JpZ2luYWwgZSBxdWUgdm9j77+9IHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vu77+9YS4gVm9j77+9IHRhbWLvv71tIGRlY2xhcmEgcXVlIG8gZGVw77+9c2l0byBkZSBzdWEgcHVibGljYe+/ve+/vW8gbu+/vW8sIHF1ZSBzZWphIGRlIHNldSBjb25oZWNpbWVudG8sIGluZnJpbmdlIGRpcmVpdG9zIGF1dG9yYWlzIGRlIG5pbmd177+9bS4KCkNhc28gYSBzdWEgcHVibGljYe+/ve+/vW8gY29udGVuaGEgbWF0ZXJpYWwgcXVlIHZvY++/vSBu77+9byBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2Pvv70gZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc++/vW8gaXJyZXN0cml0YSBkbyBkZXRlbnRvciBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgcGFyYSBjb25jZWRlciBhbyBSZXBvc2l077+9cmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7vv71hLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3Tvv70gY2xhcmFtZW50ZSBpZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBubyBjb250Ze+/vWRvIGRhIHB1YmxpY2Hvv73vv71vIG9yYSBkZXBvc2l0YWRhLgoKQ0FTTyBBIFBVQkxJQ0Hvv73vv71PIE9SQSBERVBPU0lUQURBIFRFTkhBIFNJRE8gUkVTVUxUQURPIERFIFVNIFBBVFJPQ++/vU5JTyBPVSBBUE9JTyBERSBVTUEgQUfvv71OQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PLCBWT0Pvv70gREVDTEFSQSBRVUUgUkVTUEVJVE9VIFRPRE9TIEUgUVVBSVNRVUVSIERJUkVJVE9TIERFIFJFVklT77+9TyBDT01PIFRBTULvv71NIEFTIERFTUFJUyBPQlJJR0Hvv73vv71FUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKTyBSZXBvc2l077+9cmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lKHMpIG91IG8ocykgbm9tZXMocykgZG8ocykgZGV0ZW50b3IoZXMpIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBkYSBwdWJsaWNh77+977+9bywgZSBu77+9byBmYXLvv70gcXVhbHF1ZXIgYWx0ZXJh77+977+9bywgYWzvv71tIGRhcXVlbGFzIGNvbmNlZGlkYXMgcG9yIGVzdGEgbGljZW7vv71hLgo=Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-18T20:36:04Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening |
dc.title.alternative.pt_BR.fl_str_mv |
Novos antígenos para o diagnóstico sorológico de leishmaniose visceral humana identificada por triagem imunogenômica |
title |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening |
spellingShingle |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening Ana Maria Ravena Severino Carvalho Visceral leishmaniasis Antigens Immunogenomic screen B-cell epitopes Leishmania infantum Proteins Peptides Serologic diagnosis Leishmaniose visceral Antígenos Epitopos de linfócito B Leishmania infantum Proteínas Peptídeos Testes sorológicos |
title_short |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening |
title_full |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening |
title_fullStr |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening |
title_full_unstemmed |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening |
title_sort |
New antigens for the serological diagnosis of human visceral leishmaniasis identified by immunogenomic screening |
author |
Ana Maria Ravena Severino Carvalho |
author_facet |
Ana Maria Ravena Severino Carvalho Tiago Antônio de Oliveira Mendes Eduardo Antônio Ferraz Coelho Mariana Costa Duarte Daniel Menezes Souza |
author_role |
author |
author2 |
Tiago Antônio de Oliveira Mendes Eduardo Antônio Ferraz Coelho Mariana Costa Duarte Daniel Menezes Souza |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Ana Maria Ravena Severino Carvalho Tiago Antônio de Oliveira Mendes Eduardo Antônio Ferraz Coelho Mariana Costa Duarte Daniel Menezes Souza |
dc.subject.por.fl_str_mv |
Visceral leishmaniasis Antigens Immunogenomic screen B-cell epitopes Leishmania infantum Proteins Peptides Serologic diagnosis |
topic |
Visceral leishmaniasis Antigens Immunogenomic screen B-cell epitopes Leishmania infantum Proteins Peptides Serologic diagnosis Leishmaniose visceral Antígenos Epitopos de linfócito B Leishmania infantum Proteínas Peptídeos Testes sorológicos |
dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose visceral Antígenos Epitopos de linfócito B Leishmania infantum Proteínas Peptídeos Testes sorológicos |
description |
Visceral leishmaniasis (VL) still represents a serious public health problem in Brazil due to the inefficiency of the control measures currently employed, that included early diagnosis and treatment of human cases, vector control, euthanasia of infected dogs and, recently approved in Brazil, treatment with Milteforam drug. Effective clinical management depend largely on early and unequivocal diagnosis, however, cross-reactivity have also been described in serological tests, especially when it refers to individuals from areas where Chagas’ disease is also present. Thus, to discover new antigens to improve the current serological tests for VL diagnosis is urgently needed. Here, we performed an immunogenomic screen strategy to identify conserved linear B-cell epitopes in the predicted L. infantum proteome using the following criteria: i) proteins expressed in the stages found in the vertebrate host, amastigote stage, and secreted/excreted, to guarantee greater exposure to the immune system; ii) divergent from proteins present in other infectious disease pathogens with incidence in endemic areas for VL, as T. cruzi; iii) highly antigenic to humans with different genetic backgrounds, independently of the clinical stage of the disease; iv) stable and adaptable to quality-control tests to guarantee reproducibility; v) using statistical analysis to determine a suitable sample size to evaluate accuracy of diagnostic tests established by receiver operating characteristic strategy. We selected six predicted linear B-cell epitopes from three proteins of L. infantum parasite. The results demonstrated that a mixture of peptides (Mix IV: peptides 3+6) were able to identify VL cases and simultaneously able to discriminate infections caused by T. cruzi parasite with high accuracy (100.00%) and perfect agreement (Kappa index = 1.000) with direct methods performed by laboratories in Brazil. The results also demonstrated that peptide-6, Mix III (peptides 2+6) and I (peptides 2+3+6) are potential antigens able to used in VL diagnosis, represented by high accuracy (Ac = 99.52%, 99.52% and 98.56%, respectively). This study represents an interesting strategy for discovery new antigens applied to serologic diagnosis which will contribute to the improvement of the diagnosis of VL and, consequently, may help in the prevention, control and treatment of the disease in endemic areas of Brazil. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-12-20 |
dc.date.accessioned.fl_str_mv |
2023-07-18T20:36:04Z |
dc.date.available.fl_str_mv |
2023-07-18T20:36:04Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/56648 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1371/journal.pone.0209599 |
dc.identifier.issn.pt_BR.fl_str_mv |
1932-6203 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-5569-4893 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-6804-4320 |
url |
https://doi.org/10.1371/journal.pone.0209599 http://hdl.handle.net/1843/56648 https://orcid.org/0000-0002-5569-4893 https://orcid.org/0000-0002-6681-9014 https://orcid.org/0000-0002-6804-4320 |
identifier_str_mv |
1932-6203 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Plos One |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
COLTEC - COLEGIO TECNICO |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
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