title: Absence of erythrocyte sequestration and lack of multicopy gene family expression in Plasmodium falciparum from a splenectomized malaria patient.
abstract: BACKGROUND
  To avoid spleen-dependent killing mechanisms parasite-infected erythrocytes (IE) of Plasmodium falciparum malaria patients have the capacity to bind to endothelial receptors. This binding also known as sequestration, is mediated by parasite proteins, which are targeted to the erythrocyte surface. Candidate proteins are those encoded by P. falciparum multicopy gene families, such as var, rif, stevor or PfMC-2TM. However, a direct in vivo proof of IE sequestration and expression of multicopy gene families is still lacking. Here, we report on the analysis of IE from a black African immigrant, who received the diagnosis of a malignant lymphoproliferative disorder and subsequently underwent splenectomy. Three weeks after surgery, the patient experienced clinical falciparum malaria with high parasitemia and circulating developmental parasite stages usually sequestered to the vascular endothelium such as late trophozoites, schizonts or immature gametocytes.
  
  
  RESULTS
  Initially, when isolated from the patient, the infected erythrocytes were incapable to bind to various endothelial receptors in vitro. Moreover, the parasites failed to express the multicopy gene families var, A-type rif and stevor but expression of B-type rif and PfMC-2TM genes were detected. In the course of in vitro cultivation, the parasites started to express all investigated multicopy gene families and concomitantly developed the ability to adhere to endothelial receptors such as CD36 and ICAM-1, respectively.
  
  
  CONCLUSIONS
  This case strongly supports the hypothesis that parasite surface proteins such as PfEMP1, A-type RIFIN or STEVOR are involved in interactions of infected erythrocytes with endothelial receptors mediating sequestration of mature asexual and immature sexual stages of P. falciparum. In contrast, multicopy gene families coding for B-type RIFIN and PfMC-2TM proteins may not be involved in sequestration, as these genes were transcribed in infected but not sequestered erythrocytes.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmann
authors.forename: Claudia
authors.initials: C
authors.lastname: Esser
authors.forename: Michaela
authors.initials: M
authors.lastname: Petter
authors.forename: Sabine
authors.initials: S
authors.lastname: Predehl
authors.forename: Vera
authors.initials: V
authors.lastname: von Kalckreuth
authors.forename: Stefan
authors.initials: S
authors.lastname: Schmiedel
authors.forename: Iris
authors.initials: I
authors.lastname: Bruchhaus
authors.forename: Egbert
authors.initials: E
authors.lastname: Tannich
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology* / Q000469:parasitology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000150:complications; D008288:Malaria / Q000097:blood* / Q000469:parasitology*; D020066:Merozoite Surface Protein 1 / Q000378:metabolism; D008875:Middle Aged; D005810:Multigene Family; D010963:Plasmodium falciparum / Q000378:metabolism*; D013156:Splenectomy
chemical_list: D017931:DNA Primers; D020066:Merozoite Surface Protein 1