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

<div><p>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 <i>Plasmodium vivax</i>. A total of 319 individuals living in an area of malaria transmission in the Brazilian Amazon were genotyped for four SNPs in the genes <i>CD40</i>, <i>CD40L</i>, <i>BLYS</i> and <i>CD86</i>. In addition, IgG antibodies against <i>P</i>. <i>vivax</i> apical membrane antigen 1 (PvAMA–1), Duffy binding protein (PvDBP) and merozoite surface protein 1 (PvMSP–1₁₉) were detected by ELISA. The SNP <i>BLYS</i> –871C>T was associated with the frequency of IgG responders to PvAMA–1 and PvMSP–1₁₉. The SNP <i>CD40</i> –1C>T was associated with the IgG response against PvDBP, whereas IgG antibody titers against PvMSP–1₁₉ were influenced by the polymorphism <i>CD86</i> +1057G>A. These data may help to elucidate the immunological aspects of vivax malaria and consequently assist in the design of malaria vaccines.</p></div

Summary of the epidemiological data and seropositivity of the study population.

<p>Summary of the epidemiological data and seropositivity of the study population.</p

Positive antibody response and carrier frequency of mutant alleles.

<p>Frequency of carriers of mutant alleles of SNPs in genes <i>CD40</i>, <i>BLYS</i>, <i>CD86</i>, and <i>CD40L</i> according to the number of proteins for which subjects were responders. Individuals with antibodies against the three proteins (n = 279) were classified according to their reaction against zero (n = 57), one (n = 55), two (n = 38), or three (n = 129) proteins of blood-stage <i>P</i>. <i>vivax</i>.</p

<i>BLYS</i>, <i>CD40</i>, <i>CD86</i>, and <i>CD40L</i> genotypes in relation to antibody titers against the merozoite proteins.

<p>Antibody titers were expressed as log-transformed reactivity indices (RI). For the SNP in the gene <i>CD40L</i>, men and women harboring the C allele were grouped and compared with individuals who did not possess this allele given that <i>CD40L</i> is located on chromosome X. Multivariate logistic regression analysis found no significant differences in the antibody titers between the different genotypes.</p