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红细胞血型 A 抗原水平影响肝素和 PfEMP1 抗体破坏恶性疟原虫环状体的能力。

Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes.

机构信息

Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, 171 65, Stockholm, Sweden.

Department of Infectious Diseases, Karolinska University Hospital, 171 76, Stockholm, Sweden.

出版信息

Malar J. 2021 Nov 18;20(1):441. doi: 10.1186/s12936-021-03975-w.

DOI:10.1186/s12936-021-03975-w
PMID:34794445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8600353/
Abstract

BACKGROUND

The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria. An integral part of the severe malaria pathogenesis is rosetting, the adherence of parasite infected red blood cells (RBCs) to uninfected RBCs. Rosetting is influenced by the host's ABO blood group (Bg) and rosettes formed in BgA have previously been shown to be more resilient to disruption by heparin and shield the parasite derived surface antigens from antibodies. However, data on rosetting in weak BgA subgroups is scarce and based on investigations of relatively few donors.

METHODS

An improved high-throughput flow cytometric assay was employed to investigate rosetting characteristics in an extensive panel of RBC donor samples of all four major ABO Bgs, as well as low BgA expressing samples.

RESULTS

All non-O Bgs shield the parasite surface antigens from strain-specific antibodies towards P. falciparum erythrocyte membrane protein 1 (PfEMP1). A positive correlation between A-antigen levels on RBCs and rosette tightness was observed, protecting the rosettes from heparin- and antibody-mediated disruption.

CONCLUSIONS

These results provide new insights into how the ABO Bg system affects the disease outcome and cautions against interpreting the results from the heterogeneous BgA phenotype as a single group in epidemiological and experimental studies.

摘要

背景

组织血型 ABO 系统与 COVID-19、血栓栓塞性疾病和恶性疟原虫疟疾的不良结局有关。严重疟疾发病机制的一个组成部分是红细胞(RBC)的缗钱状形成,即寄生虫感染的 RBC 与未感染的 RBC 黏附。缗钱状形成受宿主 ABO 血型(Bg)的影响,以前已经表明 BgA 中的形成的缗钱状对肝素的破坏更具抵抗力,并使寄生虫衍生的表面抗原免受抗体的影响。然而,关于弱 BgA 亚群中缗钱状形成的数据很少,并且基于对相对较少供体的调查。

方法

采用改进的高通量流式细胞术检测法,在所有四个主要 ABO Bg 以及低 BgA 表达样本的广泛 RBC 供体样本中研究了缗钱状形成的特征。

结果

所有非 O Bg 均能使寄生虫表面抗原免受针对恶性疟原虫红细胞膜蛋白 1(PfEMP1)的特异性抗体的攻击。在 RBC 上的 A 抗原水平与缗钱状紧密程度之间观察到正相关,从而保护缗钱状免受肝素和抗体介导的破坏。

结论

这些结果提供了有关 ABO Bg 系统如何影响疾病结局的新见解,并提醒人们在流行病学和实验研究中不要将异质 BgA 表型的结果解释为单一群体。

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