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.
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.
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil. Electronic address: mairabiomed@hotmail.com.
Franciele Maira Moreira Batista
FM
Tomaz
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil. Electronic address: adriana.cruz.furini@gmail.com.
Adriana Antônia
AA
da Cruz Furini
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil; Júlio de Mesquita Filho, Universidade Estadual Paulista, São José do Rio Preto, São Paulo State, Brazil. Electronic address: mpcapobianco@yahoo.com.br.
Marcela Petrolini
MP
Capobianco
Evandro Chagas Institute, MS/SVS, Ananindeua, Pará, Brazil. Electronic address: povoamm@gmail.com.
Marinete Marins
MM
Póvoa
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil. Electronic address: pamella.trindade@hotmail.com.
Pamella Cristina Alves
PC
Trindade
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil. Electronic address: valeriafraga@famerp.br.
Valéria Daltibari
VD
Fraga
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil. Electronic address: lucianamoran@famerp.br.
Luciana Moran
LM
Conceição
Júlio de Mesquita Filho, Universidade Estadual Paulista, São José do Rio Preto, São Paulo State, Brazil. Electronic address: azevedolucasr@gmail.com.
Lucas Ribeiro
LR
de Azevedo
Júlio de Mesquita Filho, Universidade Estadual Paulista, São José do Rio Preto, São Paulo State, Brazil. Electronic address: smoliani@ibilce.unesp.br.
Sônia Maria
SM
Oliani
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil; Júlio de Mesquita Filho, Universidade Estadual Paulista, São José do Rio Preto, São Paulo State, Brazil. Electronic address: gcapatti@hotmail.com.
Gustavo Capatti
GC
Cassiano
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil. Electronic address: cecavasini@famerp.br.
Carlos Eugênio
CE
Cavasini
Federal University of Pará, Institute of Biological Sciences, Belém, Pará, Brazil. Electronic address: sidneysantos@ufpa.br.
Sidney Emanuel Batista
SE
Dos Santos
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil; Júlio de Mesquita Filho, Universidade Estadual Paulista, São José do Rio Preto, São Paulo State, Brazil; Evandro Chagas Institute, MS/SVS, Ananindeua, Pará, Brazil. Electronic address: ricardomachado@iec.pa.gov.br.
Ricardo Luiz Dantas
RL
Machado
D000293:Adolescent; D000328:Adult; D000368:Aged; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000008:administration & dosage* / Q000276:immunology; D001938:Brazil / Q000453:epidemiology; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016780:Malaria, Vivax / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D008875:Middle Aged; D010966:Plasmodium vivax / Q000276:immunology*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C508598:IL4 protein, human; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; D015847:Interleukin-4
Ancestry informative markers; Interleukin 4; Parasitemia; Plasmodium vivax; SNP