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

Background 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.MethodsPolymorphisms 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.ResultsAfter 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1350-2) contains supplementary material, which is available to authorized users.

Dynamics of IgM and IgG responses to the next generation of engineered Duffy binding protein II immunogen: Strain-specific and strain-transcending immune responses over a nine-year period

“…It has been proposed that the correlation (or not) between IgG/IgM in malaria may reflect inherent structural differences between antigens, including the relative conservation of the epitopes that are targeted; for example, strong correlations between IgG and IgM was observed to MSP2, whereas this was not seen with MSP1-19 and AMA-1 [53]. In the case of P. vivax MSP1, antibody response to different regions of the protein appeared distinct, with the N-terminal portion predominantly associated with IgM antibodies and C-terminal with IgG response [54][55][56][57]. In the case of DBPII, several studies have mapped functional immunoreactive B cell epitopes associated with broadly neutralizing IgG antibody response [12,14,15,18], but no data is available about IgM response.…”

Surveillance on the Vivax Malaria in Endemic Areas in the Republic of Korea Based on Molecular and Serological Analyses

“…Malaria serological analysis of antibodies is crucial for estimating the local transmission of malaria in endemic areas, and various antigens have been used for serological and immune response analysis and antibody longevity [17][18][19][20]. In this study, PvMSP1-19, PvCSP-VK210, and PvLSA-N were used as antigens for serological analysis.…”

Association of CD28 and CTLA4 haplotypes with susceptibility to primary Sjögren′s syndrome in Mexican population

“…Different studies demonstrated that CD28 could be released in a soluble form due to alternative splicing lacking exon 3 which encodes the transmembrane region . However, it has been observed that CD28 also could be released through to membrane cleavage . Several studies have analyzed sCD28 levels in different autoimmune diseases obtaining different results .…”

“…Several studies have reported the presence of single nucleotide polymorphisms (SNPs) in both CD28 and CTLA4 genes, which could affect their expression and create isoforms of the respective protein. The CD28 −372 G>A polymorphism (rs35593994) is found at the promoter region and could abolish the independent grow factor‐1 site while the IVS3 + 17 T>C (rs3116496) is located into intron 3 near to splicing site and could create isoforms of the protein …”