Fc-fucosylation of <i>Plasmodium falciparum</i> -specific IgG varies with antigen and immunization

BACKGROUND: IgG-mediated effector functions are modulated by the antibody Fc-region glycan composition, and the absence of core fucose is a strong modifier of NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Most plasma IgG is fully Fc-fucosylated, but antigens displayed on host-derived membranes can selectively induce Fc-afucosylated IgG. These antigens include alloantigens, enveloped virus surface proteins, and PfEMP1, a malaria parasite protein expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs). METHODS: We determined levels and Fc-fucosylation of IgG specific for several P. falciparum antigens in plasma from children naturally exposed to P. falciparum and from vaccinated adults. RESULTS: IgG specific for PfEMP1 (known to be exposed on the IE surface) and PfGARP, a putative IE surface antigen, were markedly Fc-afucosylated, whereas IgG specific for antigens on parasite membranes (merozoites, gametocytes/gametes, and sporozoites) were fully Fc-fucosylated in most of the children naturally exposed to P. falciparum studied here. Immunization of adults with recombinant proteins (MSP1, Pfs230, and CSP) also consistently induced fully Fc-fucosylated IgG. Children with Fc-afucosylated PfGARP-specific IgG had reduced risk of carrying P. falciparum parasites, independent of levels of PfGARP-specific IgG. CONCLUSIONS: These results reinforce the hypothesis that Fc-afucosylation of antigen-specific IgG requires exposure of the antigen on a host membrane (context) and is a function of antigen exposure. Host-specific factors appear to play a minor role in this context.