Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida, USA.
Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Infect Dis. 2024 Jan 12;229(1):203-213. doi: 10.1093/infdis/jiad438.
Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are important targets for protective immunity. Abnormal display of PfEMP1 on the surfaces of infected erythrocytes (IEs) and reduced cytoadhesion have been demonstrated in hemoglobin (Hb) AS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria. We found that Ghanaian children with HbAS had lower levels of immunoglobulin G against several PfEMP1 variants and that this reactivity increased more slowly with age than in their HbAA counterparts. Moreover, children with HbAS have lower total parasite biomass than those with HbAA at comparable peripheral parasitemias, suggesting impaired cytoadhesion of HbAS IEs in vivo and likely explaining the slower acquisition of PfEMP1-specific immunoglobulin G in this group. In contrast, the function of acquired antibodies was comparable among Hb groups and appears to be intact and sufficient to control parasitemia via opsonization and phagocytosis of IEs.
疟原虫红细胞膜蛋白 1(PfEMP1)家族的成员是保护性免疫的重要靶标。已证明遗传性血液疾病血红蛋白(Hb)AS 和 HbAC 中存在 PfEMP1 在感染的红细胞(IE)表面的异常表达和细胞黏附减少,这些疾病与严重的恶性疟原虫疟疾的保护作用有关。我们发现,加纳 HbAS 儿童对几种 PfEMP1 变体的 IgG 水平较低,并且这种反应性随年龄的增长比 HbAA 儿童的反应性增长更慢。此外,在可比的外周寄生虫血症中,HbAS 儿童的总寄生虫生物量低于 HbAA 儿童,这表明 HbAS IE 的细胞黏附受损,这可能解释了该组中 PfEMP1 特异性 IgG 获得较慢的原因。相比之下,Hb 各组之间获得的抗体的功能相似,并且似乎完整且足以通过 IE 的调理作用和吞噬作用来控制寄生虫血症。