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Immunogenomic screening approach to identify new antigens for the serological diagnosis of chronic Chagas’ disease

  • Applied genetics and molecular biotechnology
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Abstract

Serological tests are preferentially used for the diagnosis of Chagas’ disease (CD) during the chronic phase because of the low parasitemia and high anti-Trypanosoma cruzi antibody titers. However, the current methods showed several disadvantages, as contradictory or inconclusive results, mainly related to the characteristics of the antigens used, in general, crude or whole parasites, but also due to antigen production protocol and the experimental conditions used in serological tests. Thus, better-quality serological assays are urgently needed. Here, we performed a wide immunogenomic screen strategy to identify conserved linear B-cell epitopes in the predicted proteome based on genome sequence from T. cruzi strains to will be applied as synthetic peptides in the serodiagnosis of the chronic CD. Three B-cell epitopes derived from mucin-associated surface protein (MASP) family, expressed in both infective parasite stages, trypomastigote and amastigotes, conserved in T. cruzi strains, and highly divergent as compared with Leishmania spp. proteome, were selected for this study. The results demonstrated that synthetic peptide 2 and a mixture of peptides (Mix II: peptides 2 and 3) were able to identify all chronic CD cases, indeterminate or Chagas cardiomyopathy clinical presentation, and simultaneously able to discriminate infections caused by Leishmania parasites, with high accuracy (98.37 and 100.00%, respectively) and agreement (kappa index = 0.967 and 1.000, respectively) with direct methods as compared to current diagnostic pipeline performed by reference laboratories in Brazil. This study represents an interesting strategy for the discovery of new antigens applied to serologic diagnosis of infectious diseases and for the technological development of platforms for large-scale production of diagnostic tests.

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Acknowledgments

EAFC, MORS, and DM-S thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, for fellowships.

Funding

This work was supported by grants from PRPq/UFMG (87-05/2016) and CAPES (23038.004862/2015-74).

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Authors and Affiliations

  1. Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Rutyanne Maria Tonelli Elisei, Christiane Santos Matos, Ana Maria Ravena Severino Carvalho, Ana Thereza Chaves, Kenia dos Santos Emidio, Eduardo Antonio Ferraz Coelho, Mariana Costa Duarte, Manoel Otávio da Costa Rocha & Daniel Menezes-Souza

  2. Serviço de Doenças Parasitárias, Instituto Octávio Magalhães, Fundação Ezequiel Dias (FUNED), Belo Horizonte, Minas Gerais, Brazil

    Fernanda Alvarenga Cardoso Medeiros, Ronaldo Barbosa & Andreza Pain Marcelino

  3. Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Eduardo Antonio Ferraz Coelho, Mariana Costa Duarte & Daniel Menezes-Souza

  4. Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil

    Tiago Antônio de Oliveira Mendes

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  1. Rutyanne Maria Tonelli Elisei
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  2. Christiane Santos Matos
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  3. Ana Maria Ravena Severino Carvalho
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Correspondence to Daniel Menezes-Souza.

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Ethical approval

The use of human samples was approved (protocol CAAE–66026117.3.0000.5149) by the Ethics Committee of the Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil. All patients received an individual copy of the study policy, which was reviewed by an independent person, and all participants gave their consent form in Portuguese, before blood collection. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Elisei, R.M.T., Matos, C.S., Carvalho, A.M.R.S. et al. Immunogenomic screening approach to identify new antigens for the serological diagnosis of chronic Chagas’ disease. Appl Microbiol Biotechnol 102, 6069–6080 (2018). https://doi.org/10.1007/s00253-018-8992-7

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