Lundbo, Lene Fogt4; Harboe, Zitta Barrella3; Clausen, Louise Nygaard3; Hollegaard, Mads Vilhelm3; Sørensen, Henrik Toft3; Hougaard, David Michael3; Konradsen, Helle Bossen3; Nørgaard, Mette3; Benfield, Thomas5
1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Graduate School of Health and Medical Sciences, Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Graduate School of Health and Medical Sciences, Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet5 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 2014, Vol 59, Issue 4