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Epitope mapping of the HSP83.1 protein of Leishmania braziliensis discloses novel targets for immunodiagnosis of tegumentary and visceral clinical forms of leishmaniasis.

Abstract
Gold standard serological diagnostic methods focus on antigens that elicit a strong humoral immune response that is specific to a certain pathogen. In this study, we used bioinformatics approaches to identify linear B-cell epitopes that are conserved among Leishmania species but are divergent from the host species Homo sapiens and Canis familiaris and from Trypanosoma cruzi, the parasite that causes Chagas disease, to select potential targets for the immunodiagnosis of leishmaniasis. Using these criteria, we selected heat shock protein 83.1 of Leishmania braziliensis for this study. We predicted three linear B-cell epitopes in its sequence. These peptides and the recombinant heat shock protein 83.1 (rHSP83.1) were tested in enzyme-linked immunosorbent assays (ELISAs) against serum samples from patients with tegumentary leishmaniasis (TL) and visceral leishmaniasis (VL) and from dogs infected with Leishmania infantum (canine VL [CVL]). Our data show that rHSP83.1 is a promising target in the diagnosis of TL. We also identified specific epitopes derived from HSP83.1 that can be used in the diagnosis of human TL (peptide 3), both human and canine VL (peptides 1 and 3), and all TL, VL, and CVL clinical manifestations (peptide 3). Receiver operating characteristic (ROC) curves confirmed the superior performance of rHSP83.1 and peptides 1 and 3 compared to that of the soluble L. braziliensis antigen and the reference test kit for the diagnosis of CVL in Brazil (EIE-LVC kit; Bio-Manguinhos, Fiocruz). Our study thus provides proof-of-principle evidence of the feasibility of using bioinformatics to identify novel targets for the immunodiagnosis of parasitic diseases using proteins that are highly conserved throughout evolution.
AuthorsDaniel Menezes-Souza, Tiago Antônio de Oliveira Mendes, Matheus de Souza Gomes, João Luís Reis-Cunha, Ronaldo Alves Pinto Nagem, Cláudia Martins Carneiro, Eduardo Antônio Ferraz Coelho, Lúcia Maria da Cunha Galvão, Ricardo Toshio Fujiwara, Daniella Castanheira Bartholomeu
JournalClinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 21 Issue 7 Pg. 949-59 (Jul 2014) ISSN: 1556-679X [Electronic] United States
PMID24807053 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Epitopes, B-Lymphocyte
  • Heat-Shock Proteins
  • Hsp83 protein, protozoan
  • Protozoan Proteins
Topics
  • Amino Acid Sequence
  • Animals
  • Computational Biology
  • Dog Diseases (diagnosis, immunology, parasitology)
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Epitope Mapping
  • Epitopes, B-Lymphocyte (immunology)
  • Female
  • Heat-Shock Proteins (immunology)
  • Humans
  • Immunologic Tests
  • Leishmania braziliensis (immunology)
  • Leishmania infantum (immunology)
  • Leishmaniasis, Visceral (diagnosis, immunology, veterinary)
  • Male
  • Molecular Sequence Data
  • Protozoan Proteins (immunology)
  • Sequence Alignment
  • Trypanosoma cruzi (immunology)

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