Humoral immune responses against the malaria vaccine candidate antigen Plasmodium vivax AMA-1 and IL-4 gene polymorphisms in individuals living in an endemic area of the Brazilian Amazon

Cytokine. 2015 Aug;74(2):273-8. doi: 10.1016/j.cyto.2015.03.020. Epub 2015 Apr 25.

Abstract

Background: Several studies have recently demonstrated that the immune responses against malaria is governed by different factors, including the genetic components of the host. The IL-4 gene appears to be a strong candidate factor because of its role in the regulation of the Th2 response. The present study investigated the role of IL-4 polymorphisms in the development of IgG antibodies against PvAMA-1 and the IL-4 levels in individuals infected with Plasmodium vivax in a malaria endemic area in the Brazilian Amazon.

Methods: The study sample included 83 patients who were diagnosed with P. vivax infection using thick smear and confirmed by nested-PCR. The IL-4 -590C>T and IL-4 -33C>T polymorphisms were genotyped by PCR-RFLP, and the intron 3 VNTR was genotyped by PCR. A standardised ELISA protocol was used to measure the total IgG against PvAMA-1. The cytokine/chemokine levels were measured using a Milliplex multiplex assay (Millipore). All of the subjects were genotyped with 48 ancestry informative markers to determine the proportions of African, European and Amerindian ancestry using STRUCTURE software.

Results: Of the 83 patients, 60 (73%) produced IgG antibodies against PvAMA-1. A significant decrease in the percentage of respondents was observed among the primo-infected individuals. No significant differences were observed in the frequencies of genotypes and haplotypes among individuals who were positive or negative for IgG antibodies against PvAMA-1. Furthermore, no significant correlation was observed between the IL-4 polymorphisms, antibody levels, IL-4 levels, and parasitemia.

Conclusions: This study indicated that the polymorphisms identified in the IL-4 gene are not likely to play a role in the regulation of the antibody response against PvAMA-1 and IL-4 production in vivax malaria.

Keywords: Ancestry informative markers; Interleukin 4; Parasitemia; Plasmodium vivax; SNP.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Protozoan / immunology
  • Antigens, Protozoan / administration & dosage*
  • Antigens, Protozoan / immunology
  • Brazil / epidemiology
  • Endemic Diseases*
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Interleukin-4 / genetics*
  • Interleukin-4 / immunology
  • Malaria Vaccines / administration & dosage*
  • Malaria Vaccines / immunology
  • Malaria, Vivax / epidemiology
  • Malaria, Vivax / genetics*
  • Malaria, Vivax / immunology
  • Malaria, Vivax / prevention & control
  • Male
  • Membrane Proteins / administration & dosage*
  • Membrane Proteins / immunology
  • Middle Aged
  • Plasmodium vivax / immunology*
  • Polymorphism, Genetic*
  • Protozoan Proteins / administration & dosage*
  • Protozoan Proteins / immunology
  • Th2 Cells / immunology

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • IL4 protein, human
  • Immunoglobulin G
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins
  • apical membrane antigen I, Plasmodium
  • Interleukin-4