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 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

Download Full-text

Fresh Isolates from Children with Severe Plasmodium falciparum Malaria Bind to Multiple Receptors

Infection and Immunity ◽

10.1128/iai.69.9.5849-5856.2001 ◽

2001 ◽

Vol 69 (9) ◽

pp. 5849-5856 ◽

Cited By ~ 96

Author(s):

Andreas Heddini ◽

Fredrik Pettersson ◽

Oscar Kai ◽

Juma Shafi ◽

Jack Obiero ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Severe Malaria ◽

Blood Group ◽

Adhesion Molecule ◽

Intercellular Adhesion Molecule ◽

Severity Of Disease ◽

Blood Group A ◽

Multiple Receptors ◽

Group A ◽

Adhesion Assays

ABSTRACT The sequestration of Plasmodium falciparum-infected erythrocytes (pRBC) away from the peripheral circulation is a property of all field isolates. Here we have examined the pRBC of 111 fresh clinical isolates from children with malaria for a number of adhesive features in order to study their possible coexpression and association with severity of disease. A large number of adhesion assays were performed studying rosetting, giant rosetting, and binding to CD36, intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, thrombospondin, heparin, blood group A, and immunoglobulins. Suspension assays were performed at the actual parasitemia of the isolate, while all the static adhesion assays were carried out at an equal adjusted parasitemia. The ability to bind to multiple receptors, as well as the ability to form rosettes and giant rosettes, was found to be more frequent among isolates from children with severe versus mild malaria (P = 0.0015). Rosettes and giant rosettes were more frequent for children with severe malaria, and the cell aggregates were larger and tighter, than for those with mild disease (P = 0.0023). Binding of immunoglobulins (97% of isolates) and of heparin (81% of isolates) to infected erythrocytes was common, and binding to heparin and blood group A was associated with severity of disease (P = 0.011 andP = 0.031, respectively). These results support the idea that isolates that bind to multiple receptors are involved in the causation of severe malaria and that several receptor-ligand interactions work synergistically in bringing about severe disease.

Download Full-text

Flow-Cytometric Analysis of Erythrocytic Blood Group A Antigen Density Profile

Vox Sanguinis ◽

10.1159/000461369 ◽

1991 ◽

Vol 61 (4) ◽

pp. 265-274 ◽

Cited By ~ 2

Author(s):

Zwi N. Berneman ◽

Dirk R. van Bockstaele ◽

Wim M. Uyttenbroeck ◽

Christiane Van Zaelen ◽

Joséphine Cole-Dergent ◽

...

Keyword(s):

Blood Group ◽

Density Profile ◽

Flow Cytometric Analysis ◽

Blood Group A ◽

Flow Cytometric ◽

Group A

Download Full-text

A Flow Cytometric Study of Reagent Cells to Resolve ABO Typing Discrepancy

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa117 ◽

2020 ◽

Vol 155 (1) ◽

pp. 117-123

Author(s):

Danielle L V Maracaja ◽

Jesse Qiao ◽

Tomas Salazar ◽

James Barry ◽

Karen LaForce ◽

...

Keyword(s):

Flow Cytometry ◽

Blood Group ◽

Flow Cytometric Analysis ◽

Blood Bank ◽

Blood Group A ◽

Routine Blood ◽

Flow Cytometric ◽

A Cells ◽

Group A ◽

Flow Cytometric Study

Abstract Objectives RBC alloantibodies can lead to ABO grouping discrepancies unrelated to A or B antigens or antibodies posing challenges in the blood bank testing. Routine blood bank testing and flow cytometry were used to immunophenotype reagent cells and elucidate the cause of ABO discrepancies in two patients. Methods ABO discrepancy was identified in two patients after transfusion with several units of RBCs. For both patients, the pretransfusion type and screen demonstrated blood group A. Eight and 16 days later, both patients showed an apparent antibody to reagent group A cells, which prompted additional study with patients’ samples and flow cytometric testing of commercial reagent cells. Results In both patients’ specimens, posttransfusion evaluation demonstrated an emerging antibody to the Kell antigen (K). The RBCs of both patients typed negative for K, and both were transfused with K-positive RBCs. Flow cytometric analysis of reagent RBCs demonstrated that five of seven lot numbers were positive for K. Conclusions Emerging anti-K antibody led to agglutination of the K-positive reagent A1 cells, highlighting the importance of considering RBC alloantibodies and the composition of reagent cells when interpreting cases with an apparent ABO grouping discrepancy.

Download Full-text

Correction: Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1

PLoS ONE ◽

10.1371/journal.pone.0149765 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0149765

Author(s):

Kirsten Moll ◽

Mia Palmkvist ◽

Junhong Ch'ng ◽

Mpungu Steven Kiwuwa ◽

Mats Wahlgren

Keyword(s):

Plasmodium Falciparum ◽

Blood Group ◽

Blood Group A ◽

Group A

Download Full-text

Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1

PLoS ONE ◽

10.1371/journal.pone.0145120 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0145120 ◽

Cited By ~ 21

Author(s):

Kirsten Moll ◽

Mia Palmkvist ◽

Junhong Ch'ng ◽

Mpungu Steven Kiwuwa ◽

Mats Wahlgren

Keyword(s):

Plasmodium Falciparum ◽

Blood Group ◽

Blood Group A ◽

Group A

Download Full-text

Flow-Cytometric Analysis of Erythrocytic Blood Group A Antigen Density Profile

Vox Sanguinis ◽

10.1111/j.1423-0410.1991.tb00958.x ◽

1991 ◽

Vol 61 (4) ◽

pp. 265-274 ◽

Cited By ~ 27

Author(s):

Zwi N. Berneman ◽

Dirk R. Bockstaele ◽

Wim M. Uyttenbroeck ◽

Christiane Zaelen ◽

Joséphine Cole-Dergent ◽

...

Keyword(s):

Blood Group ◽

Density Profile ◽

Flow Cytometric Analysis ◽

Blood Group A ◽

Flow Cytometric ◽

Group A

Download Full-text

Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin-like interactions.

Journal of Experimental Medicine ◽

10.1084/jem.176.5.1311 ◽

1992 ◽

Vol 176 (5) ◽

pp. 1311-1317 ◽

Cited By ~ 122

Author(s):

J Carlson ◽

M Wahlgren

Keyword(s):

Plasmodium Falciparum ◽

Blood Group ◽

Animal Species ◽

Blood Group Antigens ◽

Blood Group A ◽

Group A ◽

Group B ◽

Different Strains ◽

B Blood Group

Herein we describe an assay that was developed to quantitate the binding of normal red blood cells (RBC), labeled with carboxy fluorescein diacetate (C-FDA), to rosetting Plasmodium falciparum-infected RBC. The binding of RBC obtained from various animal species or humans to different strains or clones of rosetting P. falciparum-infected RBC was studied. A strain-specific preference of rosetting was observed for either blood group A/AB or B/AB RBC for all parasites tested. The higher affinity of rosette binding of blood group A, B, or AB vs. O RBC was reflected in larger rosettes when a given parasite was grown in RBC of the preferred blood group. The small size of the rosettes formed when P. falciparum was grown in blood group O RBC may be the in vitro correlate of the relative protection against cerebral malaria afforded by belonging to blood group O rather than to blood group A or B. Rosettes of a blood group A-preferring parasite could be completely disrupted by heparin only when grown in blood group O or B RBC, but not when grown in blood group A RBC. Similarly, the rosettes of a blood group B-preferring parasite could be more easily disrupted by heparin when grown in blood group O or A RBC than when grown in blood group B RBC. Several different saccharides inhibited rosetting of group O RBC, including two monosaccharides that are basic components of heparin. The rosetting of the same parasites grown in blood group A or B RBC was less sensitive to heparin and was specifically inhibited only by the terminal mono- and trisaccharides of the A and the B blood group antigens, the H disaccharide, and fucose. Our results suggest that rosetting is mediated by multiple lectin-like interactions, the usage of which rely on the parasite phenotype and whether the receptors are present on the host cell or not.

Download Full-text