Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first year of life.
Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first year of life.
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DOI：
10.1016/j.ijpara.2016.09.005
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发表时间：
2017-02
影响因子：
4
通讯作者：
Osier FH
中科院分区：
文献类型：
--
作者：
Murungi LM;Sondén K;Odera D;Oduor LB;Guleid F;Nkumama IN;Otiende M;Kangoye DT;Fegan G;Färnert A;Marsh K;Osier FH
严重的疟疾发作在生命的最初几个月是罕见的。脐带血IgG的衰减速率与起始浓度成反比。由脐带IgG介导的抗体依赖性呼吸爆发在婴儿期的前6个月期间保护免受严重疟疾。幼儿较不易感染严重的疟疾，但保护的目标和机制尚不清楚。脐带血抗体可能在介导保护中发挥重要作用，但许多研究已经检查了它们与感染或非严重疟疾结局的关系。在这里，我们调查了脐带血IgG恶性疟原虫裂殖子抗原和抗体介导的效应功能是否与在生命的第一年的不同时间点发展为严重疟疾的几率降低有关。我们进行了一项病例对照研究，明确的严重恶性疟疾嵌套在一个纵向出生队列的肯尼亚儿童。我们测量了脐带血总IgG水平对五个重组裂殖子抗原和抗体功能的生长抑制活性和中性粒细胞抗体依赖性呼吸爆发试验。我们还评估了母体抗体在出生后前6个月的衰减情况。平均抗体半衰期范围为2.51个月（95%置信区间（CI）：2.19-2.92）至4.91个月（95% CI：4.47-6.07）。母体抗体的下降速率与起始浓度成反比。抗体依赖性呼吸爆发活性的功能测定预测在生命的前6个月内发展为严重疟疾的几率显著降低（比值比（OR）0.07，95%CI：0.007-0.74，P = 0.007）。鉴定介导抗体依赖性呼吸爆发活性的抗体的靶点可能有助于开发在婴儿早期预防严重疟疾发作的疟疾疫苗。
Severe malaria episodes are rare during the first few months of life. The rate of decay of cord blood IgG is inversely proportional to the starting concentration. Antibody dependent respiratory burst mediated by cord IgG protects from severe malaria during the first 6 months of infancy. Young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. Cord blood antibodies may play an important role in mediating protection but many studies have examined their association with the outcome of infection or non-severe malaria. Here, we investigated whether cord blood IgG to Plasmodium falciparum merozoite antigens and antibody-mediated effector functions were associated with reduced odds of developing severe malaria at different time points during the first year of life. We conducted a case-control study of well-defined severe falciparum malaria nested within a longitudinal birth cohort of Kenyan children. We measured cord blood total IgG levels against five recombinant merozoite antigens and antibody function in the growth inhibition activity and neutrophil antibody-dependent respiratory burst assays. We also assessed the decay of maternal antibodies during the first 6 months of life. The mean antibody half-life range was 2.51 months (95% confidence interval (CI): 2.19–2.92) to 4.91 months (95% CI: 4.47–6.07). The rate of decline of maternal antibodies was inversely proportional to the starting concentration. The functional assay of antibody-dependent respiratory burst activity predicted significantly reduced odds of developing severe malaria during the first 6 months of life (Odds ratio (OR) 0.07, 95% CI: 0.007–0.74, P = 0.007). Identification of the targets of antibodies mediating antibody-dependent respiratory burst activity could contribute to the development of malaria vaccines that protect against severe episodes of malaria in early infancy.