Development of peptide-based lineage-specific serology for chronic Chagas disease: geographical and clinical distribution of epitope recognition

PLoS Negl Trop Dis. 2014 May 22;8(5):e2892. doi: 10.1371/journal.pntd.0002892. eCollection 2014 May.

Abstract

Background: Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, remains a serious public health issue in Latin America. Genetically diverse, the species is sub-divided into six lineages, known as TcI-TcVI, which have disparate geographical and ecological distributions. TcII, TcV, and TcVI are associated with severe human disease in the Southern Cone countries, whereas TcI is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a chronic infection, with cardiac and/or gastrointestinal symptoms developing years or decades after initial infection. Identifying an individual's history of T. cruzi lineage infection directly by genotyping of the parasite is complicated by the low parasitaemia and sequestration in the host tissues.

Methodology/principal findings: We have applied here serology against lineage-specific epitopes of the T. cruzi surface antigen TSSA, as an indirect approach to allow identification of infecting lineage. Chagasic sera from chronic patients from a range of endemic countries were tested by ELISA against synthetic peptides representing lineage-specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled polyethylene glycol-glycine spacer to increase rotation and ensure each amino acid side chain could freely interact with their antibodies. 79/113 (70%) of samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non-responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described elsewhere, was demonstrated here to be highly conserved across lineages and therefore not applicable to lineage-specific serology.

Conclusions/significance: These results demonstrate the considerable potential for synthetic peptide serology to investigate the infection history of individuals, geographical and clinical associations of T. cruzi lineages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Animals
  • Antibodies, Protozoan / blood
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology*
  • Chagas Disease / immunology*
  • Chagas Disease / parasitology*
  • Computational Biology
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology*
  • Serotyping / methods
  • South America
  • Triatoma / parasitology
  • Trypanosoma cruzi / classification*
  • Trypanosoma cruzi / immunology
  • Variant Surface Glycoproteins, Trypanosoma / chemistry
  • Variant Surface Glycoproteins, Trypanosoma / immunology

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes
  • Peptides
  • Variant Surface Glycoproteins, Trypanosoma
  • trypomastigote small surface antigen, Trypanosoma cruzi

Grants and funding

This work was supported by the European Commission Framework Programme Project “Comparative epidemiology of genetic lineages of Trypanosoma cruzi” ChagasEpiNet, Contract No. 223034; http://cordis.europa.eu/fp7/home_en.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.