Genetic variation and cerebrospinal fluid levels of mannose binding lectin in pneumococcal meningitis patients

PLoS One. 2013 May 31;8(5):e65151. doi: 10.1371/journal.pone.0065151. Print 2013.

Abstract

It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05-64.1; p = 0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39-3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Case-Control Studies
  • Female
  • Genetic Association Studies
  • Genetic Variation*
  • Genotype
  • Humans
  • Male
  • Mannose-Binding Lectin / cerebrospinal fluid*
  • Mannose-Binding Lectin / genetics*
  • Meningitis, Pneumococcal / cerebrospinal fluid*
  • Meningitis, Pneumococcal / complications
  • Meningitis, Pneumococcal / genetics*
  • Middle Aged
  • Odds Ratio
  • Patient Outcome Assessment
  • Polymorphism, Genetic
  • Prospective Studies

Substances

  • MBL2 protein, human
  • Mannose-Binding Lectin

Grants and funding

This study has been funded by grants from The Netherlands Organization for Health Research and Development (ZonMw; NWO-Veni grant 2006 [916.76.023], NWO-Vidi grant [016.116.358] to DvdB, NWOVeni grant 2012 [916.130.78] to MCB), the Academic Medical Center (AMC Fellowship 2008 to DvdB), and the European Research Council (ERC Starting Grant to DvdB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.