Antibodies to variant antigens on the surfaces of infected erythrocytes are associated with protection from malaria in Ghanaian children

Antibodies to variant antigens on the surfaces of infected erythrocytes are associated with protection from malaria in Ghanaian children
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DOI:
10.1128/iai.69.6.3713-3718.2001
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发表时间:
2001-06-01
影响因子:
3.1
通讯作者:
Theander, TG
Theander, TG
中科院分区:
医学2区
文献类型:
--
作者:
Dodoo, D;Staalsoe, T;Theander, TG

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恶性疟原虫红细胞膜蛋白1(Plasmodiumfalciparumerythrocyte membrane protein 1,PfEMP 1)是一种表达于感染红细胞表面的变异抗原,每个疟原虫基因组含有约40个PfEMP 1基因,但在特定时间只有1个PfEMP 1基因表达。PfEMP 1作为内皮细胞的寄生虫隔离配体,使寄生虫能够避免脾通道,PfEMP 1抗体可以通过抑制隔离来保护疾病,从而促进脾脏中受感染红细胞的破坏,在这项研究中,我们已经测量了加纳儿童对PfEMP 1保守区的抗体,通过流式细胞术检测恶性疟原虫田间分离株感染的红细胞上的连接免疫吸附试验和变异分子抗体,基于密切的临床监测,这些儿童被分为在季节期间患有疟疾的儿童(易感染)和未患有疟疾的儿童(未受保护)。保守的PfEMP 1肽和变异表位的抗体的患病率大于50%,免疫球蛋白G(IgG)的水平与年龄相关。保守肽和变异表位的抗体水平均高于易感儿童。校正年龄的影响后,IgG水平的变体抗原的苏丹和加纳寄生虫分离株仍然显着高于易感儿童的保护。因此,受感染的红细胞表面表达的针对变体抗原的IgG水平与预防临床疟疾相关。相反,来自PfEMP 1保守部分的肽的IgG水平与疟疾保护无关。
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a variant antigen expressed on the surface of infected erythrocytes, Each parasite genome contains about 40 PfEMP1 genes, but only 1 PfEMP1 gene is expressed at a given time. PfEMP1 serves as a parasite-sequestering ligand to endothelial cells and enables the parasites to avoid splenic passage, PfEMP1 antibodies may protect from disease by inhibiting sequestration, thus facilitating the destruction of infected erythrocytes in the spleen, In this study, we have measured antibodies in Ghanaian children to a conserved region of PfEMP1 by enzyme-linked immunosorbent assay and antibodies to variant molecules on erythrocytes infected with field isolates of P. falciparum by flow cytometry, Based on close clinical monitoring, the children were grouped into those who did (susceptible) and those who did not (protected) have malaria during the season. The prevalences of antibodies to both the conserved PfEMP1 peptide and the variant epitopes were greater than 50%, and the levels of immunoglobulin G (IgG) correlated with age. The levels of antibodies to both the conserved peptide and the variant epitopes were higher in protected than in susceptible children. After correcting for the effect of age, the levels of IgG to variant antigens on a Sudanese and a Ghanaian parasite isolate remained significantly higher in protected than in susceptible children. Thus; the levels of IgG to variant antigens expressed on the surface of infected erythrocytes correlated with protection from clinical malaria. In contrast, the levels of IgG to a peptide derived from a conserved part of PfEMP1 did not correlate with protection from malaria.