Mannose-binding lectin gene, MBL2, polymorphisms are not associated with susceptibility to invasive pneumococcal disease in children.
BACKGROUND
Most children are transiently colonized with Streptococcus pneumoniae, but very few develop invasive pneumococcal disease (IPD). Host genetic variation of innate immunity may predispose to IPD. We investigated the effect of genetic variation in the mannose-binding lectin gene, MBL2, on susceptibility and disease severity of IPD in previously healthy children aged <5 years.


METHODS
IPD cases were identified through national registries. DNA was obtained from the Danish Neonatal Screening Biobank. Pneumococcal serotypes were determined by Quellung reaction. The associations between MBL2 diplotypes and IPD susceptibility, serotypes, and outcome were investigated using logistic regression analysis.


RESULTS
We included 372 cases with meningitis, 907 with bacteremia, and 1263 age- and sex-matched controls; 2372 individuals were successfully genotyped and assigned MBL2 diplotypes. The median age in our combined case series was 13 months. Children with defective diplotypes were not at higher risk for meningitis than children with other diplotypes (odds ratio [OR], 0.85; 95% confidence interval [CI], .56-1.28). Similar results were found for bacteremia (OR, 0.89; 95% CI, .68-1.15) as well as for all cases (OR, 0.87; 95% CI, .70-1.09). There was no association with susceptibility to recurrent IPD (n = 12) for children with defective diplotypes compared with cases with a single episode (OR, 0.53; 95% CI, .07-4.13) and with all controls (OR, 0.46; 95% CI, .06-3.56). There was no association between diplotypes and mortality or between diplotypes and pneumococcal serotypes.


CONCLUSIONS
Defective MBL2 polymorphisms did not predict increased IPD susceptibility in children born in Northern Europe.
Department of Infectious Diseases Clinical Research Centre, Hvidovre Hospital, University of Copenhagen, Hvidovre Faculty of Health Sciences, University of Copenhagen, Copenhagen.
Lene Fogt
LF
Lundbo
Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
Zitta Barrella
ZB
Harboe
Department of Infectious Diseases Clinical Research Centre, Hvidovre Hospital, University of Copenhagen, Hvidovre.
Louise Nygaard
LN
Clausen
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen.
Mads Vilhelm
MV
Hollegaard
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus.
Henrik Toft
HT
Sørensen
Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen.
David Michael
DM
Hougaard
Department of Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
Helle Bossen
HB
Konradsen
Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus.
Mette
M
Nørgaard
Department of Infectious Diseases Clinical Research Centre, Hvidovre Hospital, University of Copenhagen, Hvidovre Faculty of Health Sciences, University of Copenhagen, Copenhagen.
Thomas
T
Benfield
D002675:Child, Preschool; D003718:Denmark; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D011008:Pneumococcal Infections / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000145:classification / Q000302:isolation & purification
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin
MBL deficiency; MBL2 genotypes; invasive pneumococcal disease; pneumococcal serotypes