title: Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1.
abstract: The ABO blood group antigens are expressed on erythrocytes but also on endothelial cells, platelets and serum proteins. Notably, the ABO blood group of a malaria patient determines the development of the disease given that blood group O reduces the probability to succumb in severe malaria, compared to individuals of groups A, B or AB. P. falciparum rosetting and sequestration are mediated by PfEMP1, RIFIN and STEVOR, expressed at the surface of the parasitized red blood cell (pRBC). Antibodies to these antigens consequently modify the course of a malaria infection by preventing sequestration and promoting phagocytosis of pRBC. Here we have studied rosetting P. falciparum and present evidence of an immune evasion mechanism not previously recognized. We find the accessibility of antibodies to PfEMP1 at the surface of the pRBC to be reduced when P. falciparum forms rosettes in blood group A RBC, as compared to group O RBC. The pRBC surrounds itself with tightly bound normal RBC that makes PfEMP1 inaccessible to antibodies and clearance by the immune system. Accordingly, pRBC of in vitro cloned P. falciparum devoid of ABO blood group dependent rosetting were equally well detected by anti-PfEMP1 antibodies, independent of the blood group utilized for their propagation. The pathogenic mechanisms underlying the severe forms of malaria may in patients of blood group A depend on the ability of the parasite to mask PfEMP1 from antibody recognition, in so doing evading immune clearance.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, SE-171 77 Stockholm, Sweden.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moll
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, SE-171 77 Stockholm, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Palmkvist
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, SE-171 77 Stockholm, Sweden.
authors.forename: Junhong
authors.initials: J
authors.lastname: Ch'ng
authors.affiliation: Department of Pediatrics, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.|Department of Biochemistry, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Mpungu Steven
authors.initials: MS
authors.lastname: Kiwuwa
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Box 280, Nobels väg 16, SE-171 77 Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D006801:Humans; D057131:Immune Evasion; D007075:Immunoglobulin M / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000276:immunology*; D012397:Rosette Formation
chemical_list: D000017:ABO Blood-Group System; D000913:Antibodies, Protozoan; D007075:Immunoglobulin M; D015800:Protozoan Proteins