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伊朗不稳定疟疾流行区 Fcγ 受体 IIa(cd32)基因多态性与抗疟原虫无性血期抗原 IgG 亚类抗体的分析。

Analysis of Fcgamma receptor IIa (cd32) gene polymorphism and anti-malarial IgG subclass antibodies to asexual blood-stage antigen of Plasmodium falciparum in an unstable malaria endemic area of Iran.

机构信息

Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, P.O. Box 1316943551, Tehran, Iran.

出版信息

Exp Parasitol. 2013 May;134(1):115-21. doi: 10.1016/j.exppara.2013.02.012. Epub 2013 Feb 28.

Abstract

One of the main host genetic factors involved in inflammation, immune responses and pathogenesis of malaria is FcγRIIa (cd32) gene. A single point mutation at position 131 replace an arginine (R) with a histidine (H) that can affect the affinity of the receptor for human IgG subclasses. This investigation was designed to explore the polymorphisms at FcγRIIa gene in association with both anti-malarial total IgG antibody and IgG subclass profiles to C-terminal region of Plasmodium falciparum merozoite surface protein 1 (PfMSP-1(19)). In this study, 166 infected patients with P. falciparum who are living in a malaria endemic area of Iran were studied using PCR-RFLP and ELISA methods. The results showed that the frequency of FcγRIIa-R/R131, -R/H131 and -H/H131 genotypes was 9.6%, 42.8% and 47.6%, respectively. Level of total IgG to recombinant PfMSP-1(19) antigen showed that there was no difference among the FcγRIIa-R/R131, -R/H131 and -H/H131 groups. With regards to the IgG subclasses, the anti-malarial IgG1 antibodies predominated. Also, there was a significant difference between the frequency of positive responders for anti-PfMSP-1(19) IgG and IgG1 antibodies in P. falciparum-infected individuals with FcγRIIa-R/R131, -R/H131 or -H/H131 genotypes (P<0.05, X(2) test). Regarding to IgG2-PfMSP-1(19) antibody, 27.27% (FcγRIIa-R/R131), 25.71% (FcγRIIa-R/H131) and 22.2% (FcγRIIa-H/H131) of IgG responders showed positive antibody response. Taken together, this study is the first report that exhibits the high frequency of both FcγRIIa-H131H genotypes and H131 allele in the Baluchi ethnic group, which was similar to the Fulani ethnic group. The present results provide additional data to understand the role of FcγRIIa-131 genotypes in the pathogenesis of malaria.

摘要

FcγRIIa(CD32)基因是参与炎症、免疫反应和疟疾发病机制的主要宿主遗传因素之一。位于 131 位的单个点突变将精氨酸(R)替换为组氨酸(H),这可能会影响受体对人 IgG 亚类的亲和力。本研究旨在探讨 FcγRIIa 基因多态性与抗疟总 IgG 抗体和 IgG 亚类对恶性疟原虫裂殖体表面蛋白 1(PfMSP-1(19))C 末端区的关系。在这项研究中,使用 PCR-RFLP 和 ELISA 方法对 166 名居住在伊朗疟疾流行地区的恶性疟原虫感染患者进行了研究。结果表明,FcγRIIa-R/R131、-R/H131 和 -H/H131 基因型的频率分别为 9.6%、42.8%和 47.6%。重组 PfMSP-1(19)抗原的总 IgG 水平表明,FcγRIIa-R/R131、-R/H131 和 -H/H131 组之间没有差异。关于 IgG 亚类,抗疟 IgG1 抗体占优势。此外,FcγRIIa-R/R131、-R/H131 或 -H/H131 基因型的恶性疟原虫感染个体中,抗 PfMSP-1(19) IgG 和 IgG1 抗体的阳性反应者频率存在显著差异(P<0.05,X(2)检验)。关于 IgG2-PfMSP-1(19)抗体,27.27%(FcγRIIa-R/R131)、25.71%(FcγRIIa-R/H131)和 22.2%(FcγRIIa-H/H131)的 IgG 应答者表现出阳性抗体反应。总之,本研究首次报道了在俾路支族中 FcγRIIa-H131H 基因型和 H131 等位基因的高频率,这与富拉尼族相似。本研究结果为了解 FcγRIIa-131 基因型在疟疾发病机制中的作用提供了额外的数据。

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