Endoglin in African children with Plasmodium falciparum malaria: a novel player in severe malaria pathogenesis?
BACKGROUND
Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria-specifically, cerebral malaria-are still unclear. Transforming growth factor beta (TGF-beta) family members are important regulators of inflammation that influence malaria pathogenesis. The soluble form of the auxiliary receptor endoglin (sEng) may play a role in malaria pathogenesis.


METHODS
Serum levels of sEng were measured using enzyme-linked immunosorbent-assay in Gabonese children with cerebral malaria (n = 7) severe malaria (n = 43), or uncomplicated malaria (n = 43) and were compared with levels in healthy control subjects (n = 25) and in another infectious disease group (n = 8).


RESULTS
Serum sEng levels were higher in patients with cerebral malaria and all patients with severe malaria when compared with levels in patients in the other infection group and the healthy control group. Furthermore, sEng correlated significantly with disease severity. Only 7% of patients with uncomplicated malaria and none of the control patients (patients in the other infection group or the healthy control group) had serum levels higher than 12 ng/mL, whereas this was found in 85.7% of patients with cerebral malaria and 46.5% of patients with severe malaria.


CONCLUSIONS
High sEng levels may attenuate anti-inflammatory response resulting in clinical deterioration of patients with P. falciparum malaria. Our results further corroborate the role of the vascular compartment, especially the endothelium, in severe malaria pathogenesis.
Dietmann
Anelia
A
Clinical Department of Neurology, Innsbruck Medical University, 6020 Innsbruck, Austria. Anelia.Dietmann@i-med.ac.at
Helbok
Raimund
R
Lackner
Peter
P
Fischer
Marlene
M
Reindl
Markus
M
Lell
Bertrand
B
Issifou
Saadou
S
Kremsner
Peter G
PG
Schmutzhard
Erich
E
D000349:Africa; D000818:Animals; D015703:Antigens, CD / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation; D016778:Malaria, Falciparum / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000097:blood*; D012720:Severity of Illness Index
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface