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G6PD A 变体影响对恶性疟原虫 MSP2 的抗体应答。

G6PD A-variant influences the antibody responses to Plasmodium falciparum MSP2.

机构信息

Institut de Recherche pour le Développement (IRD), Unité Mixte de Recherche (UMR) 216 Mère et enfant face aux infections tropicales, 75006 Paris, France.

出版信息

Infect Genet Evol. 2011 Aug;11(6):1287-92. doi: 10.1016/j.meegid.2011.04.016. Epub 2011 Apr 22.

DOI:10.1016/j.meegid.2011.04.016
PMID:21549219
Abstract

High antibody levels directed to Plasmodium falciparum merozoite surface proteins (MSP), including MSP2, as well as genetically related red blood cell defects, have previously been found to be associated with protection against malaria. Here, our main objective was to study the changes in MSP2-specific total IgG, IgG1 and IgG3 responses during a malaria transmission season in order to assess the impact of sickle-cell, α(+)-thalassemia and G6PD variants on antibody kinetics. Repeated parasitological assessments of a cohort of children were conducted during an 8-month period. Antibody responses to recombinant MSP2/3D7 and MSP2/FC27 proteins were measured at the beginning and at the end of transmission season. We found that (i) the period of last Plasmodium falciparum infection during the transmission season was associated with IgG3 anti-MSP2 change. Compared to the IgG3 levels of children infected in January 2003 (end of transmission season), the IgG3 level of children decreased with the length of the period without infection, (ii) G6PD A- carriers had a lower increase of IgG3 levels to MSP2/FC27 and MSP2/3D7 during the transmission season than the noncarriers. This latter finding is suggestive of qualitative and/or quantitative reduction of exposure to malarial antigens related to this genetic variant, leading to weaker stimulation of specific antibody responses. We speculate that cell-mediated immune activity may explain the clinical protection afforded by this genetic trait.

摘要

高抗体水平针对恶性疟原虫裂殖子表面蛋白(MSP),包括 MSP2,以及遗传相关的红细胞缺陷,以前被发现与疟疾的保护作用有关。在这里,我们的主要目的是研究在疟疾传播季节期间 MSP2 特异性总 IgG、IgG1 和 IgG3 反应的变化,以评估镰状细胞、α(+)-地中海贫血和 G6PD 变异对抗体动力学的影响。在 8 个月的时间里,对一组儿童进行了反复的寄生虫学评估。在传播季节开始和结束时,测量了对重组 MSP2/3D7 和 MSP2/FC27 蛋白的抗体反应。我们发现:(i)传播季节期间最后一次感染恶性疟原虫的时期与 IgG3 抗 MSP2 的变化有关。与 2003 年 1 月(传播季节结束时)感染的儿童的 IgG3 水平相比,感染儿童的 IgG3 水平随无感染期的延长而降低;(ii)在传播季节期间,G6PD A- 携带者对 MSP2/FC27 和 MSP2/3D7 的 IgG3 水平增加低于非携带者。后一种发现提示与这种遗传变异相关的疟原抗原的暴露质量和/或数量减少,导致特异性抗体反应的刺激减弱。我们推测细胞介导的免疫活性可以解释这种遗传特征所提供的临床保护作用。

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