Cassiano Gustavo Capatti, Furini Adriana A C, Capobianco Marcela P, Storti-Melo Luciane M, Almeida Maria E, Barbosa Danielle R L, Póvoa Marinete M, Nogueira Paulo A, Machado Ricardo L D
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.
Malar J. 2016 Jun 3;15:306. doi: 10.1186/s12936-016-1350-2.
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.
针对无性血液期疟原虫蛋白质的体液免疫反应与临床免疫相关。然而，抗体驱动反应的变化可能与人类宿主的遗传成分有关。本研究的目的是评估免疫系统共刺激分子基因多态性对针对间日疟原虫疫苗候选抗原的体液免疫反应强度的影响。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对巴西亚马逊地区一个流行区178例间日疟原虫感染患者的CD28、CTLA4、ICOS、CD40、CD86和BLYS基因多态性进行基因分型。通过酶联免疫测定法测定针对ICB2-5（即间日疟原虫裂殖子表面蛋白1（PvMSP-1）的N端部分）的IgM、总IgG和IgG亚类水平。通过逻辑回归模型评估多态性与抗体反应之间的关联。
在进行多重检验校正后，CD28单核苷酸多态性rs3116496隐性个体的IgG1水平显著更高（p = 0.00004）。此外，CD28 rs35593994与BLYS rs9514828之间的相互作用对IgM水平有影响（p = 0.0009）。
本研究结果支持以下假设：免疫系统共刺激成分基因的多态性可促成针对间日疟原虫抗原的天然抗体驱动反应。
