Loss of complement regulatory proteins on uninfected erythrocytes in vivax and falciparum malaria anemia.
Loss of complement regulatory proteins on uninfected erythrocytes in vivax and falciparum malaria anemia.
复制标题
间日疟和恶性疟贫血中未感染红细胞上补体调节蛋白的丢失。
DOI：
10.1172/jci.insight.124854
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发表时间：
2018
期刊：
影响因子：
8
通讯作者：
Boyle,MichelleJ
中科院分区：
文献类型：
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作者：
Oyong,DamianA;Kenangalem,Enny;Poespoprodjo,JeanneR;Beeson,JamesG;Anstey,NicholasM;Price,RicN;Boyle,MichelleJ
贫血是疟疾的主要并发症，主要是由感染期间未受感染的红细胞损失引起的。红细胞通过补体调节蛋白（CRP）丢失而清除是恶性疟原虫感染时贫血的重要原因，但其在间日疟原虫感染中的作用尚不清楚。CRP损失增加RBC对巨噬细胞清除的易感性，这一过程也受CD47调节。我们比较了来自印度尼西亚巴布亚的间日疟和恶性疟以及不同贫血严重程度的成人患者感染和未感染红细胞上的CRP和CD 47表达。通过ELISA测定补体激活和寄生虫特异性补体结合抗体。在恶性疟和间日疟的严重贫血中，CR1和CD55的水平降低。CRP和CD47的丢失仅限于未感染的RBC，感染的RBC具有更高的表达。补体结合抗体、补体激活和CRP丢失之间无相关性。我们的研究结果表明，CRP的损失是一个泛物种，年龄无关的机制疟疾贫血。感染的红细胞上CRP和CD47表达水平较高，表明寄生虫受到补体介导的破坏和巨噬细胞清除的保护。保护性抗体和CRP损失之间缺乏关联突出了补体致病和保护途径是感染期间不同的机制。
Anemia is a major complication of malaria, driven largely by loss of uninfected RBCs during infection. RBC clearance through loss of complement regulatory proteins (CRPs) is a significant contributor to anemia in Plasmodium falciparum infection, but its role in Plasmodium vivax infection is unknown. CRP loss increases RBC susceptibility to macrophage clearance, a process that is also regulated by CD47. We compared CRPs and CD47 expression on infected and uninfected RBCs in adult patients with vivax and falciparum malaria and different anemia severities from Papua, Indonesia. Complement activation and parasite-specific complement-fixing antibodies were measured by ELISA. Levels of CR1 and CD55 were reduced in severe anemia in both falciparum and vivax malaria. Loss of CRPs and CD47 was restricted to uninfected RBCs, with infected RBCs having higher expression. There was no association among complement-fixing antibodies, complement activation, and CRP loss. Our findings demonstrate that CRP loss is a pan-species, age-independent mechanism of malarial anemia. Higher levels of CRP and CD47 expression on infected RBCs suggest that parasites are protected from complement-mediated destruction and macrophage clearance. Lack of associations between protective antibodies and CRP loss highlight that complement pathogenic and protective pathways are distinct mechanisms during infection.