Blood Group A Antigen Is a Coreceptor in Plasmodium falciparum Rosetting

Abstract

The malaria parasite Plasmodium falciparum utilizes molecules present on the surface of uninfected red blood cells (RBC) for rosette formation, and a dependency on ABO antigens has been previously shown. In this study, the antirosetting effect of immune sera was related to the blood group of the infected human host. Sera from malaria-immune blood group A (or B) individuals were less prone to disrupt rosettes from clinical isolates of blood group A (or B) patients than to disrupt rosettes from isolates of blood group O patients. All fresh clinical isolates and laboratory strains exhibited distinct ABO blood group preferences, indicating that utilization of blood group antigens is a general feature of P. falciparum rosetting. Soluble A antigen strongly inhibited rosette formation when the parasite was cultivated in A RBC, while inhibition by glycosaminoglycans decreased. Furthermore, a soluble A antigen conjugate bound to the cell surface of parasitized RBC. Selective enzymatic digestion of blood group A antigen from the uninfected RBC surfaces totally abolished the preference of the parasite to form rosettes with these RBC, but rosettes could still form. Altogether, present data suggest an important role for A and B antigens as coreceptors in P. falciparum rosetting.Although erythrocytes have traditionally been considered relatively inert containers of hemoglobin, mounting evidence suggests that they in fact bear numerous surface molecules that are active in microbial attachment processes (22). The asexual stages of the malaria parasite Plasmodium falciparum utilize molecules on the surface of uninfected red blood cells (RBC) for rosette formation, i.e., binding of parasite-infected RBC (pRBC) to uninfected RBC. Rosetting has been associated with the occurrence of severe malaria, i.e., cerebral malaria and anemia (5,14,17,18). The P. falciparum erythrocyte membrane protein 1 (PfEMP1), a member of a family of highmolecular-weight polypeptides encoded by the var genes (4, 20, 21), has been identified as a rosetting ligand (8,19). Various host receptors on the surface of uninfected RBC have been proposed, including ABO blood group antigens (7), CD36 (11), CD35 (19), and heparan sulfate (HS) or HS-like molecules (3,8). Still, little is known about the relative contribution of different receptors in rosetting and their prevalence in nature. Previous studies have implicated the ABO blood group type in rosetting (1, 18, 24) and strain-specific blood group preferences for rosette formation have been described previously (7).In this study, we examine the utilization of ABO blood group antigens for rosette formation in laboratory strains and fresh clinical isolates. We assess the antirosetting effect of hyperimmune sera in relation to the ABO blood group type and examine the relationship of the A antigen to the rosetting phenotype. MATERIALS AND METHODSPatients, parasites, and sera. Two P. falciparum strains, FCR3S1 (a blood group A-preferring line [7] cloned by limiting dilution from FCR3S, which originated from the FCR s...

The surface variant antigens of Plasmodium falciparum contain cross-reactive epitopes

“…As a consequence, antibodies induced by infection are clone-specific. This was shown clearly by acute and convalescent sera from children (1, 4, 6, 9), sera from experimentally infected Aotus monkeys (7), and sera from individuals living in areas of low or seasonal transmission (2,3,28). Even antibodies from malaria-immune African adults are variantspecific; the same antibodies only rarely will cross-agglutinate PEs from two variant clones (10).…”

“…However, the variant nature of PfEMP1 remains the major obstacle for vaccine development, as the immune response to PfEMP1 is highly variant-specific. Individuals with relatively low exposure to P. falciparum parasites show very restricted recognition of the PE surface (1,2,4,6). This is even more pronounced in sera from monkeys repeatedly exposed to a particular P. falciparum strain that recognize exclusively the PfEMP1 of that strain (7).…”

“…Antibodies to PfEMP1 show significant correlation with development of clinical immunity, making PfEMP1 an important vaccine candidate (1)(2)(3)(4)(5). However, the variant nature of PfEMP1 remains the major obstacle for vaccine development, as the immune response to PfEMP1 is highly variant-specific.…”

The association of genetic markers and malaria infection in the Brazilian Western Amazonian region

“…It is known that parasitized erythrocytes form rosettes more readily with red blood cells of either A, B or AB groups than with those belonging to blood group O (Udomsangpetch et al 1989,1993, Carlson & Wahlgren 1992, Barragan et al 2000, and that, in Zimbawe, blood group A was associated with both lower hemoglobin levels and severe central nervous system malaria with coma (Fisher & Boone 1998). In spite of the fact that these phenomena might provoke an association of ABO blood groups and the number of malarial episodes, the results presented above do not enable to reject the null hypothesis that this polymorphic system is not associated with the number of malarial episodes.…”

“…), has significant associations with several red blood cell polymorphisms (hemoglobin, glucose-6-phosphate dehydrogenase, ABO and Duffy systems) detected in populations who are or were living under hyper-endemic conditions in the Old World (Allison 1954a,b, Vandepitte & Delaisse 1957, Motulsky 1960, 1964, Siniscalco et al 1961, Miller et al 1976, Santos et al 1983, Udomsangpetch et al 1989, 1993, Carlson & Wahlgren 1992, Barragan et al 2000. The Amazon region, characterized by an hypo-endemic pattern of infection, due mainly to its low demographic index, provides an excellent field to test hypotheses on the generalization of these associations, as well as to investigate the existence of other associations due to either different mechanisms or to linkage disequilibria between genetic markers and genes involved with susceptibility/resistance to Plasmodium infection.…”