Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3.

Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3.
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DOI:
10.1186/s12936-015-0658-7
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发表时间:
2015-04-16
期刊:
影响因子:
3
通讯作者:
Pied S
Pied S
中科院分区:
医学3区
文献类型:
--
作者:
Guiyedi V;Bécavin C;Herbert F;Gray J;Cazenave PA;Kombila M;Crisanti A;Fesel C;Pied S

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无症状恶性疟原虫携带者对疟疾的后天保护机制仅部分了解。其中,自身反应性抗体所起的作用尚未明确。在这项研究中,在无症状的恶性疟原虫感染的加蓬儿童中,研究了循环自身反应性和寄生虫特异性免疫球蛋白 G (IgG) 之间的关系、它们与细胞因子水平的相关性以及它们与预防疟疾的关联。使用蛋白质微阵列免疫测定法分析恶性疟原虫特异性抗体库的多样性,通过定量免疫印迹法分析总自身抗体库,并通过 ELISA 测量地方性对照(EC)和来自加蓬的恶性疟原虫感染的无症状疟疾(AM)或轻度疟疾(MM)儿童的循环细胞因子水平。使用单连锁层次聚类、Kruskal-Wallis 检验和 Spearman 等级相关性评估自身和寄生虫特异性抗体库与循环细胞因子的关联。 AM 儿童表现出对裂殖子表面蛋白 3 (MSP3) 的 IgG 反应,但对 MSP1-19 没有反应,尽管他们的恶性疟原虫特异性 IgG 总水平与 MM 组相似。此外,无症状儿童识别脑抗原的自身抗体水平升高。此外,在 AM 和 MM 儿童中发现 IL-10 水平与寄生虫负载之间存在相关性。这两组人群的血浆 IL-10 和 IFN-γ 水平与年龄以及总血浆 IgG 水平之间也表现出显着相关性。 IL-10 和 IFN-γ 水平也与 AM 中的自身抗体反应相关。总而言之,这些结果表明,与 MSP3 IgG 增加以及 IL-10 和 IFN-γ 血浆水平升高相关的自身反应性多克隆反应可能有助于加蓬儿童无症状恶性疟原虫感染时触发的保护性免疫机制。本文的在线版本 (doi:10.1186/s12936-015-0658-7) 包含补充材料,可供授权用户使用。
Mechanisms of acquired protection to malaria in asymptomatic Plasmodium falciparum carriers are only partially understood. Among them, the role plays by the self-reactive antibodies has not been clarified yet. In this study, the relationship between repertoires of circulating self-reactive and parasite-specific immunoglobulin G (IgG), their correlation with cytokine levels, and their association with protection against malaria was investigated in asymptomatic Plasmodium falciparum-infected Gabonese children. The diversity of P. falciparum-specific antibody repertoire was analysed using a protein micro-array immunoassay, the total auto-antibody repertoire by quantitative immunoblotting and circulating cytokine levels were measured by ELISA in endemic controls (EC) and P. falciparum-infected children from Gabon with asymptomatic (AM) or mild malaria (MM). The association of self- and parasite-specific antibody repertoires with circulating cytokines was evaluated using single linkage hierarchical clustering, Kruskal – Wallis tests and Spearman’s rank correlation. Children with AM exhibited an IgG response to merozoite surface protein 3 (MSP3) but not to MSP1-19, although their levels of total P. falciparum-specific IgG were similar to those in the MM group. Moreover, the asymptomatic children had increased levels of autoantibodies recognising brain antigens. In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children. These two groups also exhibited significant correlations between plasma levels of IL-10 and IFN-γ with age and with total plasma IgG levels. IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM. Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children. The online version of this article (doi:10.1186/s12936-015-0658-7) contains supplementary material, which is available to authorized users.
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