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

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 uninfe...

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Autores principales:	Pontus Hedberg, Madle Sirel, Kirsten Moll, Mpungu Steven Kiwuwa, Petter Höglund, Ulf Ribacke, Mats Wahlgren
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Malaria Plasmodium falciparum Rosetting Histo-blood group ABO system Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/97aa16a7bd47439d99c9d4aa4b2545ab
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spelling	oai:doaj.org-article:97aa16a7bd47439d99c9d4aa4b2545ab2021-11-21T12:33:49ZRed blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes10.1186/s12936-021-03975-w1475-2875https://doaj.org/article/97aa16a7bd47439d99c9d4aa4b2545ab2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12936-021-03975-whttps://doaj.org/toc/1475-2875Abstract 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. Graphical AbstractPontus HedbergMadle SirelKirsten MollMpungu Steven KiwuwaPetter HöglundUlf RibackeMats WahlgrenBMCarticleMalariaPlasmodium falciparumRosettingHisto-blood group ABO systemArctic medicine. Tropical medicineRC955-962Infectious and parasitic diseasesRC109-216ENMalaria Journal, Vol 20, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Malaria Plasmodium falciparum Rosetting Histo-blood group ABO system Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216
spellingShingle	Malaria Plasmodium falciparum Rosetting Histo-blood group ABO system Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Pontus Hedberg Madle Sirel Kirsten Moll Mpungu Steven Kiwuwa Petter Höglund Ulf Ribacke Mats Wahlgren Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
description	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. Graphical Abstract
format	article
author	Pontus Hedberg Madle Sirel Kirsten Moll Mpungu Steven Kiwuwa Petter Höglund Ulf Ribacke Mats Wahlgren
author_facet	Pontus Hedberg Madle Sirel Kirsten Moll Mpungu Steven Kiwuwa Petter Höglund Ulf Ribacke Mats Wahlgren
author_sort	Pontus Hedberg
title	Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
title_short	Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
title_full	Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
title_fullStr	Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
title_full_unstemmed	Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
title_sort	red blood cell blood group a antigen level affects the ability of heparin and pfemp1 antibodies to disrupt plasmodium falciparum rosettes
publisher	BMC
publishDate	2021
url	https://doaj.org/article/97aa16a7bd47439d99c9d4aa4b2545ab
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Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes

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