Abstract
BackgroundThe 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.MethodsAn 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.ResultsAll 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.ConclusionsThese 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.Graphical
Highlights
The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria
Rosetting is mediated by PfEMP1, RIFIN and STEVOR, parasite ligands that interact with a plethora of red blood cells (RBCs) receptors such as BgA, complement receptor 1 (CR1) and glycophorin C (GYPC) [12,13,14,15]
The current paper explores the effect of all four ABO blood group (Bg) on P. falciparum rosetting, with a particular emphasis on low A antigen expression levels
Summary
The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria. Besides a wide range of parasite factors, several human host genetic factors have been shown to influence the susceptibility to SM, including the sickle-cell trait, α+-thalassaemia and the histo-blood group (Bg) ABO system [3,4,5,6]. Many of these have been evolutionary selected for in human populations in malaria endemic regions, which highlights the influence this disease has on the trade-off between risk and benefit for human adaptation [7]. BgA-mediated rosetting has been suggested to confer protection from the immune system of the host, by preventing exposure of important immunogenic parasite-derived epitopes at the RBC surface [17]
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