Mannose-binding lectin variant associated with severe malaria in young African children.
Mannose-binding lectin (MBL) is a serum protein which initiates innate immune responses to microbial pathogens by binding to non-self surface oligosaccharides. MBL deficiency is the most common congenital immunodeficiency of human and has been shown to predispose to infections, particularly in children and immune compromised. In a matched case-control study among 870 Ghanaian children, we examined the influence of six polymorphisms of the MBL2 gene on Plasmodium falciparum infection and severe malaria. A missense mutation resulting in low MBL activity (MBL2*C) was found in 35% of healthy controls, but in 42% of asymptomatically infected children (P=0.01), and in 46% of patients with severe malaria (P=0.007). Heterozygosity for MBL2*C was associated with increased odds of infection (odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.1), severe malaria (OR, 1.7; 95% CI, 1.2-2.4), and of severe anemia in particular (OR, 2.3; 95% CI, 1.4-3.8). The population attributable fraction of severe malaria cases attributable to MBL2*C heterozygosity was 17%. Our results suggest that the MBL pathway of the complement system is a critical determinant of both, susceptibility to P. falciparum infection and manifestation of severe malaria, particularly in young children in whom specific immune responses are weak or absent.
Holmberg
Ville
V
Institute of Tropical Medicine and International Health, Charité-University Medicine Berlin, Spandauer Damm 130, 14050 Berlin, Germany. ville.holmberg@helsinki.fi
Schuster
Friederike
F
Dietz
Ekkehart
E
Sagarriga Visconti
J Chantale
JC
Anemana
Sylvester D
SD
Bienzle
Ulrich
U
Mockenhaupt
Frank P
FP
D000740:Anemia; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005869:Ghana; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008288:Malaria / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000276:immunology*; D011110:Polymorphism, Genetic; D011485:Protein Binding
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin