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

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.
AuthorsRutyanne Maria Tonelli Elisei, Christiane Santos Matos, Ana Maria Ravena Severino Carvalho, Ana Thereza Chaves, Fernanda Alvarenga Cardoso Medeiros, Ronaldo Barbosa, Andreza Pain Marcelino, Kenia Dos Santos Emidio, Eduardo Antonio Ferraz Coelho, Mariana Costa Duarte, Tiago Antônio de Oliveira Mendes, Manoel Otávio da Costa Rocha, Daniel Menezes-Souza
JournalApplied microbiology and biotechnology (Appl Microbiol Biotechnol) Vol. 102 Issue 14 Pg. 6069-6080 (Jul 2018) ISSN: 1432-0614 [Electronic] Germany
PMID29736822 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes, B-Lymphocyte
  • Proteome
Topics
  • Antibodies, Protozoan (blood)
  • Antigens, Protozoan (genetics, immunology)
  • Brazil
  • Chagas Disease (diagnosis, immunology)
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping
  • Epitopes, B-Lymphocyte (immunology)
  • Genomics
  • Humans
  • Proteome
  • Serologic Tests
  • Trypanosoma cruzi (genetics, immunology)

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