Age-dependent association of human mannose-binding lectin mutations with susceptibility to invasive meningococcal disease in childhood.
BACKGROUND
Mannose-binding lectin (MBL) is an important factor of the innate immune system, and MBL-initiated complement activation is an important early defense mechanism against various bacterial infections, including invasive meningococcal disease.


METHODS
In a pediatric cohort (ages 2-215 months) with invasive meningococcal disease, we investigated the overall and age-stratified frequency of 3 MBL exon 1 variations (C154T, G161A, G170A), previously shown to result in markedly decreased MBL plasma concentrations, by allele specific fluorescent hybridization probe real-time PCR assays and direct sequencing. Healthy age-matched volunteers with the same ethnic background and no history of meningococcal disease served as a control group.


RESULTS
The overall frequency of a MBL exon 1 variant genotype was significantly higher in patients than in controls (31.8% vs. 8.2%, P < 0.001). In the patient group with disease onset less than 24 months of age, the prevalence of MBL structural variant genotype was further increased (39.3%; P < 0.001) and most pronounced in children with disease onset less than 12 months of age (57.1%; P < 0.001) when compared with healthy controls. Analysis of clinical severity and outcome revealed no significant difference between patients with wild-type and mutant alleles.


CONCLUSIONS
Our data suggest that MBL exon 1 structural variants are significantly associated with susceptibility to childhood meningococcal disease in an age-dependent manner.
Faber
Joerg
J
Children's Hospital, Johannes Gutenberg-University, Mainz, Germany. jorg.faber@childrens.harvard.edu
Schuessler
Therese
T
Finn
Adam
A
Murdoch
Craig
C
Zenz
Werner
W
Habermehl
Pirmin
P
Meyer
Claudius U
CU
Zabel
Bernhard U
BU
Schmitt
Heinz
H
Zepp
Fred
F
Knuf
Markus
M
D000293:Adolescent; D000375:Aging / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008589:Meningococcal Infections / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D015995:Prevalence
D037601:Mannose-Binding Lectin