Polymorphisms in B Cell Co-Stimulatory Genes Are Associated with IgG Antibody Responses against Blood–Stage Proteins of Plasmodium vivax

Abstract

The development of an effective immune response can help decrease mortality from malaria and its clinical symptoms. However, this mechanism is complex and has significant inter-individual variation, most likely owing to the genetic contribution of the human host. Therefore, this study aimed to investigate the influence of polymorphisms in genes involved in the costimulation of B-lymphocytes in the naturally acquired humoral immune response against proteins of the asexual stage of Plasmodium vivax. A total of 319 individuals living in an area of malaria transmission in the Brazilian Amazon were genotyped for four SNPs in the genes CD40, CD40L, BLYS and CD86. In addition, IgG antibodies against P. vivax apical membrane antigen 1 (PvAMA–1), Duffy binding protein (PvDBP) and merozoite surface protein 1 (PvMSP–119) were detected by ELISA. The SNP BLYS –871C>T was associated with the frequency of IgG responders to PvAMA–1 and PvMSP–119. The SNP CD40 –1C>T was associated with the IgG response against PvDBP, whereas IgG antibody titers against PvMSP–119 were influenced by the polymorphism CD86 +1057G>A. These data may help to elucidate the immunological aspects of vivax malaria and consequently assist in the design of malaria vaccines.

Immunogenetic markers associated with a naturally acquired humoral immune response against an N-terminal antigen of Plasmodium vivax merozoite surface protein 1 (PvMSP-1)

“…The present study was conducted in the municipality of Goianésia do Pará, Pará state, Brazil, which is a constituent of the Brazilian Amazon region, where P. vivax is responsible for more than 80 % of all malaria cases [ 35 ]. Details of the study area have been described elsewhere [ 36 ]. Cross-sectional surveys conducted from February 2011 to August 2012 were used to recruit 178 subjects (125 men and 53 women) presenting with classic symptoms of malaria, who sought treatment at the medical service of the municipality; the subjects had an average age of 29.8 years (varying from 14 to 68 years).…”

“…All single nucleotide polymorphisms (SNPs) were genotyped by PCR-restriction fragment length polymorphism (RFLP). The SNPs − 372G > A and + 17T > C in CD28 (rs35593994 and rs3116496, respectively), − 318C > T and + 49A > G in CTLA4 (rs5742909 and rs231775, respectively), + 1564T > C in ICOS (rs4404254), + 1057G > A in CD86 (rs1129055), − 1C > T in CD40 (rs1883832), and − 871C > T in BLYS (rs9514828) were genotyped according to previously described protocols [ 36 , 38 , 39 ]. Primer sequences, restriction enzymes, and the restriction fragments obtained of each SNP are presented in Additional file 1 .…”

Cytokine gene polymorphisms are not associated with anti-PvDBP, anti-PvAMA-1 or anti-PvMSP-119 IgG antibody levels in a malaria-endemic area of the Brazilian Amazon

“…Ninety samples from vivax malaria-infected subjects and 51 samples from uninfected subjects were collected in Goianésia do Pará (03°50′33″S; 49°05′49″ W). The subjects were in a sub-group of individuals previously analysed by Cassiano et al [ 10 ]. The study has evaluated the effect of genetic ancestry on the distribution of polymorphisms in the TNFA , IFNG and IL10 genes (unpublished data).…”

“…PvDBP antibodies inhibit interactions with the Duffy antigen receptor for chemokines (DARC) in erythrocytes [ 8 ], and antibodies produced against PvMSP-1 19 have been shown to prevent merozoite invasion in vitro [ 9 ]. The synthesis of immunoglobulins is complex and depends on the process of antigen presentation by B lymphocytes (BL) to TCD4 lymphocytes and the involvement of co-stimulatory molecules and their receptors [ 10 ].…”

“…In Goianésia do Pará, a municipality located in the Brazilian Amazon, two studies evaluated the effects of polymorphisms in genes involved in the humoral immune response. Cassiano et al [ 10 ] found that the frequency of specific IgG responders against PvAMA-1, PvDBP and PvMSP-1 19 was associated with polymorphisms in the BLYS (−871C > T), CD40 (−1C > T) and CD86 (+1057G > A) genes. In contrast, genotypes and haplotypes of the IL4 gene were not associated with the production of PvAMA-1 antibodies [ 18 ].…”