Tomaz Franciele Maira Moreira Batista, da Cruz Furini Adriana Antônia, Capobianco Marcela Petrolini, Póvoa Marinete Marins, Trindade Pamella Cristina Alves, Fraga Valéria Daltibari, Conceição Luciana Moran, de Azevedo Lucas Ribeiro, Oliani Sônia Maria, Cassiano Gustavo Capatti, Cavasini Carlos Eugênio, Dos Santos Sidney Emanuel Batista, Machado Ricardo Luiz Dantas
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil.
Microorganism Research Center, Department of Dermatological, Infectious, and Parasitic Diseases, Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil; Júlio de Mesquita Filho, Universidade Estadual Paulista, São José do Rio Preto, São Paulo State, Brazil.
Cytokine. 2015 Aug;74(2):273-8. doi: 10.1016/j.cyto.2015.03.020. Epub 2015 Apr 25.
Several studies have recently demonstrated that the immune responses against malaria is governed by different factors, including the genetic components of the host. The IL-4 gene appears to be a strong candidate factor because of its role in the regulation of the Th2 response. The present study investigated the role of IL-4 polymorphisms in the development of IgG antibodies against PvAMA-1 and the IL-4 levels in individuals infected with Plasmodium vivax in a malaria endemic area in the Brazilian Amazon.
The study sample included 83 patients who were diagnosed with P. vivax infection using thick smear and confirmed by nested-PCR. The IL-4 -590C>T and IL-4 -33C>T polymorphisms were genotyped by PCR-RFLP, and the intron 3 VNTR was genotyped by PCR. A standardised ELISA protocol was used to measure the total IgG against PvAMA-1. The cytokine/chemokine levels were measured using a Milliplex multiplex assay (Millipore). All of the subjects were genotyped with 48 ancestry informative markers to determine the proportions of African, European and Amerindian ancestry using STRUCTURE software.
Of the 83 patients, 60 (73%) produced IgG antibodies against PvAMA-1. A significant decrease in the percentage of respondents was observed among the primo-infected individuals. No significant differences were observed in the frequencies of genotypes and haplotypes among individuals who were positive or negative for IgG antibodies against PvAMA-1. Furthermore, no significant correlation was observed between the IL-4 polymorphisms, antibody levels, IL-4 levels, and parasitemia.
This study indicated that the polymorphisms identified in the IL-4 gene are not likely to play a role in the regulation of the antibody response against PvAMA-1 and IL-4 production in vivax malaria.
最近的几项研究表明，针对疟疾的免疫反应受多种因素调控，包括宿主的遗传成分。白细胞介素-4（IL-4）基因似乎是一个重要的候选因素，因为它在Th2反应调节中发挥作用。本研究调查了IL-4基因多态性在巴西亚马逊疟疾流行地区间日疟原虫感染个体中抗PvAMA-1 IgG抗体产生及IL-4水平方面的作用。
研究样本包括83例经厚血膜涂片诊断为间日疟原虫感染并经巢式PCR确认的患者。采用PCR-RFLP对IL-4 -590C>T和IL-4 -33C>T多态性进行基因分型，采用PCR对内含子3 VNTR进行基因分型。使用标准化ELISA方案检测抗PvAMA-1的总IgG。使用Milliplex多重检测法（密理博）测量细胞因子/趋化因子水平。所有受试者均用48个祖先信息标记进行基因分型，以使用STRUCTURE软件确定非洲、欧洲和美洲印第安人祖先的比例。
83例患者中，60例（73%）产生了抗PvAMA-1的IgG抗体。初感染个体中应答者百分比显著降低。抗PvAMA-1 IgG抗体阳性或阴性个体的基因型和单倍型频率无显著差异。此外，IL-4多态性、抗体水平、IL-4水平和寄生虫血症之间未观察到显著相关性。
本研究表明，IL-4基因中鉴定出的多态性不太可能在间日疟原虫疟疾中抗PvAMA-1抗体反应和IL-4产生的调节中发挥作用。
