A biomarker for tegumentary and visceral leishmaniasis based on a recombinant Leishmania hypothetical protein

Immunobiology. 2019 Jul;224(4):477-484. doi: 10.1016/j.imbio.2019.05.008. Epub 2019 May 30.

Abstract

The measures for leishmaniasis control include the precise diagnosis of disease. However, although several recombinant antigens have been tested with this biotechnological purpose, no effective product exists, which could detects patients with the active disease, as well as differentiates them from cured and treated patients. In this study, a conserved Leishmania hypothetical protein, which was identified in Leishmania infantum parasites, but evaluated to presents high homology in the amino acid sequences between distinct parasite species, was evaluated for the diagnosis of tegumentary and visceral leishmaniasis. In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant. Regarding the serological analyses, ELISA experiments using the recombinant protein (rLiHyL) and a human serological panel revealed high sensitivity and specificity values to detect both diseases, while control antigens showed worst results. Regarding the cellular response, results showed that rLiHyL-stimulated cells produced higher IFN-γ and lower IL-4 and IL-10 levels in the supernatants. Also, the anti-protein antibody production was evaluated in these patients, and data showed higher IgG2 and lower IgG1 levels found in the treated patients and healthy controls, demonstrating the stimulation of a Th1-type response induced by the rLiHyL protein. In conclusion, this hypothetical protein can be considered as antigenic in TL and VL, as well as a vaccine candidate to be tested in future studies to protect against disease.

Keywords: Antibodies; Cytokines; Hypothetical proteins; Immunogenicity; Leishmaniasis; Serodiagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • Biomarkers
  • Case-Control Studies
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Leishmaniasis, Visceral / diagnosis
  • Leishmaniasis, Visceral / immunology*
  • Leishmaniasis, Visceral / parasitology
  • Male
  • Middle Aged
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Recombinant Proteins*
  • Serologic Tests

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Biomarkers
  • Cytokines
  • Immunoglobulin G
  • Protozoan Proteins
  • Recombinant Proteins