Lopez-Perez Mary, Viwami Firmine, Seidu Zakaria, Jensen Anja T R, Doritchamou Justin, Ndam Nicaise Tuikue, Hviid Lars
Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
UMR 261 MERIT, Université de Paris, Institut de Recherche pour le Développement, Paris, France.
Open Forum Infect Dis. 2021 Nov 15;8(12):ofab527. doi: 10.1093/ofid/ofab527. eCollection 2021 Dec.
Sickle cell trait (HbAS) protects against severe malaria but not against placental malaria (PM). In this study, erythrocyte membrane protein (PfEMP1)-specific antibodies were measured in HbAA and HbAS Beninese pregnant women as a proxy of exposure to specific PfEMP1 variants.
Plasma samples collected at delivery from 338 HbAA and 63 HbAS women were used to measure immunoglobulin (Ig)G levels to 6 recombinant PfEMP1 proteins and 3 corresponding native proteins expressed on the infected erythrocyte (IE) surface. Immunoglobulin G-mediated inhibition of VAR2CSA IEs adhesion to chondroitin sulfate A (CSA) was also tested.
Levels of PfEMP1-specific IgG were similar in the 2 groups, except for native IT4VAR09 on IEs, where IgG levels were significantly higher in HbAS women. Adjusted odds ratios for women with positive IgG to HB3VAR06 and PFD1235w suggest a lower risk of infection with these virulent variants among HbAS individuals. The percentage of IEs binding to CSA did not differ between HbAA and HbAS women, but it correlated positively with levels of anti-VAR2CSA and parity. Women with PM had lower levels of anti-VAR2CSA-specific IgG and lower IgG-mediated inhibition of IE adhesion to CSA.
The findings support similar malaria exposure in HbAA and HbAS women and a lack of HbAS-dependent protection against placental infection among pregnant women.
镰状细胞性状（HbAS）可预防重症疟疾，但不能预防胎盘疟疾（PM）。在本研究中，检测了贝宁HbAA和HbAS孕妇中红细胞膜蛋白（PfEMP1）特异性抗体，以此作为接触特定PfEMP1变体的替代指标。
收集338名HbAA和63名HbAS孕妇分娩时的血浆样本，用于检测针对6种重组PfEMP1蛋白和3种在感染红细胞（IE）表面表达的相应天然蛋白的免疫球蛋白（Ig）G水平。还测试了免疫球蛋白G介导的对VAR2CSA IE与硫酸软骨素A（CSA）黏附的抑制作用。
两组中PfEMP1特异性IgG水平相似，但IE上的天然IT4VAR09除外，HbAS女性的IgG水平显著更高。IgG对HB3VAR06和PFD1235w呈阳性的女性的校正比值比表明，HbAS个体感染这些毒性变体的风险较低。HbAA和HbAS女性中与CSA结合的IE百分比无差异，但与抗VAR2CSA水平和产次呈正相关。患有PM的女性抗VAR2CSA特异性IgG水平较低，且IgG介导的对IE与CSA黏附的抑制作用较低。
研究结果支持HbAA和HbAS女性疟疾暴露情况相似，且HbAS对孕妇胎盘感染缺乏依赖性保护作用。
