title: Plasmodium falciparum glycosylphosphatidylinositol toxin interacts with the membrane of non-parasitized red blood cells: a putative mechanism contributing to malaria anemia.
abstract: Following exposure to synthetic Plasmodium falciparum glycosylphosphatidylinositol (P.f.-GPI), red blood cells (RBCs) reacted with antibodies in the serum of a patient with severe acute P. falciparum malaria. Carbohydrate microarray analysis of the patient's serum confirmed the presence of both, IgM and IgG antibodies against P.f.-GPI. The antibodies failed to bind to RBCs when P.f.-GPI lacking the lipid portion was applied. Addition of the detergent Triton X-100 during preincubation with P.f.-GPI resulted in increased recognition. Recognition of P.f.-GPI was dependent on the concentrations of synthetic P.f.-GPI, the serum and the numbers of RBCs. IgM antibodies dominated P.f.-GPI-sensitized RBCs recognition. Recognition by IgM antibodies proved highest during the 1st week of acute malaria and decreased during the following 2 weeks as assessed by flow cytometry and carbohydrate microarray analysis. These results strongly support the notion that released P.f.-GPI can insert into non-parasitized RBC membranes and results in recognition by circulating anti-GPI antibodies and possibly subsequent elimination. This process may contribute to malaria-associated anemia.
authors.affiliation: Section Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. nbrattig@bni-hamburg.de
authors.forename: Norbert W
authors.initials: NW
authors.lastname: Brattig
authors.forename: Katharina
authors.initials: K
authors.lastname: Kowalsky
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.forename: Gerd D
authors.initials: GD
authors.lastname: Burchard
authors.forename: Faustin
authors.initials: F
authors.lastname: Kamena
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
mesh_terms: D000740:Anemia; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D002462:Cell Membrane / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects*; D017261:Glycosylphosphatidylinositols / Q000633:toxicity*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008288:Malaria / Q000473:pathology; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D013997:Time Factors; D037521:Virulence Factors / Q000633:toxicity*
chemical_list: D000913:Antibodies, Protozoan; D017261:Glycosylphosphatidylinositols; D007075:Immunoglobulin M; D037521:Virulence Factors