title: Immunogenetic markers associated with a naturally acquired humoral immune response against an N-terminal antigen of Plasmodium vivax merozoite surface protein 1 (PvMSP-1).
abstract: Humoral immune responses against proteins of asexual blood-stage malaria parasites have been associated with clinical immunity. However, variations in the antibody-driven responses may be associated with a genetic component of the human host. The objective of the present study was to evaluate the influence of co-stimulatory molecule gene polymorphisms of the immune system on the magnitude of the humoral immune response against a Plasmodium vivax vaccine candidate antigen.
  
  
  
  Polymorphisms in the CD28, CTLA4, ICOS, CD40, CD86 and BLYS genes of 178 subjects infected with P. vivax in an endemic area of the Brazilian Amazon were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The levels of IgM, total IgG and IgG subclasses specific for ICB2-5, i.e., the N-terminal portion of P. vivax merozoite surface protein 1 (PvMSP-1), were determined by enzyme-linked immuno assay. The associations between the polymorphisms and the antibody response were assessed by means of logistic regression models.
  
  
  
  After correcting for multiple testing, the IgG1 levels were significantly higher in individuals recessive for the single nucleotide polymorphism rs3116496 in CD28 (p = 0.00004). Furthermore, the interaction between CD28 rs35593994 and BLYS rs9514828 had an influence on the IgM levels (p = 0.0009).
  
  
  
  The results of the present study support the hypothesis that polymorphisms in the genes of co-stimulatory components of the immune system can contribute to a natural antibody-driven response against P. vivax antigens.
authors.affiliation: Department of Biology, São Paulo State University, São José Do Rio Preto, São Paulo, Brazil. gcapatti@hotmail.com.|Department of Skin, Infectious and Parasitic Diseases, São José do Rio Preto Medical School, São José Do Rio Preto, São Paulo, Brazil. gcapatti@hotmail.com.
authors.forename: Gustavo Capatti
authors.initials: GC
authors.lastname: Cassiano
authors.affiliation: Department of Skin, Infectious and Parasitic Diseases, São José do Rio Preto Medical School, São José Do Rio Preto, São Paulo, Brazil.
authors.forename: Adriana A C
authors.initials: AA
authors.lastname: Furini
authors.affiliation: Department of Biology, São Paulo State University, São José Do Rio Preto, São Paulo, Brazil.|Department of Skin, Infectious and Parasitic Diseases, São José do Rio Preto Medical School, São José Do Rio Preto, São Paulo, Brazil.
authors.forename: Marcela P
authors.initials: MP
authors.lastname: Capobianco
authors.affiliation: Department of Biology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil.
authors.forename: Luciane M
authors.initials: LM
authors.lastname: Storti-Melo
authors.affiliation: Leônidas and Maria Deane Institute, Oswaldo Cruz Foundation, Manaus, Amazonas, Brazil.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Almeida
authors.affiliation: Laboratory of Malaria Basic Research, Division of Parasitology, Evandro Chagas Institute, Belém, Pará, Brazil.
authors.forename: Danielle R L
authors.initials: DR
authors.lastname: Barbosa
authors.affiliation: Laboratory of Malaria Basic Research, Division of Parasitology, Evandro Chagas Institute, Belém, Pará, Brazil.
authors.forename: Marinete M
authors.initials: MM
authors.lastname: Póvoa
authors.affiliation: Leônidas and Maria Deane Institute, Oswaldo Cruz Foundation, Manaus, Amazonas, Brazil.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Nogueira
authors.affiliation: Department of Biology, São Paulo State University, São José Do Rio Preto, São Paulo, Brazil.|Department of Skin, Infectious and Parasitic Diseases, São José do Rio Preto Medical School, São José Do Rio Preto, São Paulo, Brazil.|Laboratory of Malaria Basic Research, Division of Parasitology, Evandro Chagas Institute, Belém, Pará, Brazil.
authors.forename: Ricardo L D
authors.initials: RL
authors.lastname: Machado
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D001938:Brazil; D003430:Cross-Sectional Studies; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007125:Immunogenetics; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D007155:Immunologic Factors / Q000235:genetics*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D010966:Plasmodium vivax / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007155:Immunologic Factors; D020066:Merozoite Surface Protein 1
keywords: Antibodies; ICB2-5; Immunogenetics; MSP-1; Plasmodium vivax