Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako, P.O Box 1805, Bamako, Mali.
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, USA.
Malar J. 2019 Apr 11;18(1):128. doi: 10.1186/s12936-019-2764-4.
Plasmodium falciparum-infected erythrocytes (IE) sequester in deep vascular beds where their adhesion is mediated by an array of endothelial surface receptors. Because parasite adhesion has been associated with disease, antibodies that block this activity may confer protective immunity. Here, levels of plasma anti-adhesion activity and surface reactivity against freshly collected IEs from malaria-infected children were measured in a Malian birth cohort and related to child age and malaria infection history.
Plasma samples from children enrolled at birth in a longitudinal cohort study of mother-infant pairs in Ouelessebougou, Mali were collected at multiple time points during follow-up visits. Anti-adhesion antibodies (i.e., inhibit IE binding to any of several endothelial receptors) and reactivity with surface IE proteins were measured using a binding inhibition assay and by flow cytometry, respectively.
Levels of antibodies that inhibit the binding of children's IE to the receptors ICAM-1, integrin αβ and laminin increased with age. The breadth of antibodies that inhibit ICAM-1 and laminin adhesion (defined as the proportion of IE isolates whose binding was reduced by ≥ 50%) also significantly increased with age. The number of malaria infections prior to plasma collection was associated with levels of plasma reactivity to IE surface proteins, but not levels of anti-adhesion activity.
Age is associated with increased levels of antibodies that reduce adhesion of children's IE to three of the ten endothelial receptors evaluated here. These results suggest that anti-adhesion antibodies to some but not all endothelial receptors are acquired during the first few years of life.
恶性疟原虫感染的红细胞（IE）在深部血管床中定殖，其黏附由一系列内皮表面受体介导。由于寄生虫黏附与疾病有关，因此阻断这种活性的抗体可能赋予保护性免疫。在这里，我们测量了马里出生队列中疟疾感染儿童的新鲜采集 IE 血浆中的抗黏附活性和表面反应性，并将其与儿童年龄和疟疾感染史相关联。
在马里 Ouelessebougou 的母婴纵向队列研究中，在出生时入组的儿童的血浆样本在随访期间的多个时间点收集。使用结合抑制测定法和流式细胞术分别测量抗黏附抗体（即抑制 IE 与几种内皮受体结合的抗体）和与 IE 表面蛋白的反应性。
抑制儿童 IE 与受体 ICAM-1、整合素 αβ 和层粘连蛋白结合的抗体水平随年龄增长而增加。抑制 ICAM-1 和层粘连蛋白黏附的抗体广度（定义为结合减少≥50%的 IE 分离株比例）也随年龄显著增加。在采集血浆之前的疟疾感染次数与 IE 表面蛋白的血浆反应性水平相关，但与抗黏附活性水平无关。
年龄与降低儿童 IE 与这里评估的十个内皮受体中的三个结合的抗体水平增加有关。这些结果表明，针对一些但不是所有内皮受体的抗黏附抗体是在生命的头几年获得的。
