Expression of the domain cassette 8 Plasmodium falciparum erythrocyte membrane protein 1 is associated with cerebral malaria in Benin.
BACKGROUND
Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a highly polymorphic adherence receptor expressed on the surface of infected erythrocytes. Based on sequence homology PfEMP-1 variants have been grouped into three major groups A-C, the highly conserved VAR2CSA variants, and semi-conserved types defined by tandem runs of specific domains ("domain cassettes" (DC)). The PfEMP-1 type expressed determines the adherence phenotype, and is associated with clinical outcome of infection.


METHODS
Parasite isolates from Beninese children or women presenting with, respectively, CM or PAM were collected along with samples from patients with uncomplicated malaria (UM). We assessed the transcript level of var genes by RT-qPCR and the expression of PfEMP-1 proteins by LC-MS/MS.


RESULTS
Var genes encoding DC8 and Group A PfEMP-1 were transcribed more often and at higher levels in cerebral malaria vs. uncomplicated malaria patients. LC-MS/MS identified peptides from group A, DC8 PfEMP-1 more frequently in cerebral malaria than in uncomplicated malaria and pregnancy-associated malaria samples.


CONCLUSIONS
This is the first study to show association between PfEMP-1 subtype and disease outcome by direct analysis of parasites proteome. The results corroborate that group A and specifically the PfEMP-1 types DC8 are universally associated with cerebral malaria. This is a crucial observation for promoting studies on malaria pathogenesis.
Institut de Recherche pour le Développement (IRD), UMR216-Mère et enfant face aux infections tropicales, Paris, France.
Gwladys I
GI
Bertin
Thomas
T
Lavstsen
François
F
Guillonneau
Justin
J
Doritchamou
Christian W
CW
Wang
Jakob S
JS
Jespersen
Sem
S
Ezimegnon
Nadine
N
Fievet
Maroufou J
MJ
Alao
Francis
F
Lalya
Achille
A
Massougbodji
Nicaise Tuikue
NT
Ndam
Thor G
TG
Theander
Philippe
P
Deloron
D000293:Adolescent; D000328:Adult; D001541:Benin; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D005260:Female; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006801:Humans; D016779:Malaria, Cerebral / Q000235:genetics / Q000469:parasitology*; D013058:Mass Spectrometry; D010963:Plasmodium falciparum / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000235:genetics / Q000469:parasitology; D017434:Protein Structure, Tertiary; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D015800:Protozoan Proteins; D012333:RNA, Messenger; C085731:erythrocyte membrane protein 1, Plasmodium falciparum