Dzwonek, A.B.; (2008) The role of mannose binding lectin (MBL) in paediatric infection. Doctoral thesis , University of London.

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Abstract

Mannose-binding lectin (MBL) is a circulating pattern-recognition molecule that recognizes microbial carbohydrate motifs leading to complement activation and cell lysis. Mutations in MBL promoter and exon-1 result in reduced protein levels and in a number of studies appear to increase susceptibility to infection. This thesis explores the role of MBL in paediatric infection in two clinical settings. The effect of MBL deficiency on susceptibility and progression of HIV-1 infection was investigated in one hundred and twenty eight children, aged 2-16 years. MBL deficiency appeared to be less frequent in this population than in published series of Caucasian or African children. This may be due to selective survival of children with wild type MBL genotypes as patients with severe disease, as assessed by low CD4+T cell counts, were more likely to have MBL variant alleles. In support of this hypothesis, MBL deficiency was less frequent in children classified as long term non- progressors (LTNP-s). A second study explored the impact of MBL on susceptibility and severity of infection in preterm neonates. One hundred sixty six preterm neonates were genotyped for MBL mutations by polymerase chain reaction (PCR) and heteroduplex analyses. Serum MBL levels were measured by ELISA. Comparison of genotypes (A= wild type, 0=variant alleles) and protein levels between groups was performed using Chi-square, Mann-Whitney or Kruskal-Wallis test. Low MBL levels were observed in premature neonates, particularly in the first week of life (p=0.001). MBL deficiency was associated with an increased risk of sepsis in VLBW neonates (<1500g), (p=0.0T). The studies described in this thesis provide support for MBL having a role in susceptibility to and severity of infection in children.

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