SummaryMannose-binding lectin (MBL) is a component of innate immunity and thus particularly important in neonates in whom adaptive immunity is not yet completely developed. Promoter polymorphisms and structural exon-1 mutations in the MBL2 gene cause reduced or deficient MBL plasma concentrations. The aim of our study was to determine the prevalence of MBL deficiency in neonates admitted to the neonatal intensive care unit (NICU). Eighty-five NICU patients (69 premature) were included in the study. We measured MBL concentrations in umbilical cord and neonatal blood within 24 h after birth by ELISA technique. MBL2 genotypes ( n = = = = 67) were determined by Taqman analysis. MBL concentrations were measured longitudinally during three weeks in 26 premature neonates. The association between pre-and intra-partum clinical data and MBL concentrations was investigated. At birth, 29 (42%) premature and six (38%) term neonates had MBL plasma concentrations ≤ ≤ ≤ ≤ 0·7 µ µ µ µ g/ml which was regarded as deficient. Twenty-one (38%) premature and four (36%) term neonates had variant MBL2 haplotypes, corresponding to exon-1 mutations and the LXPA haplotype. MBL concentrations increased over time in neonates with wild-type MBL2 haplotypes, but not in neonates with variant haplotypes. Low MBL plasma concentrations were related to lower gestational age and variant MBL2 haplotypes. Umbilical cord and neonatal MBL plasma concentrations appeared to be similar. In conclusion, almost half of our NICU patients, especially the premature ones, were MBLdeficient at birth. These infants may be at increased risk of neonatal infections. MBL concentration can reliably be measured in umbilical cord blood and it is positively correlated with gestational and postnatal age.

Mannose-binding lectin (MBL) is a serum protein of the innate immune system. After binding to a microorganism, MBL in complex with MBL-associated serine proteases activates the complement system, resulting in cleavage of complement factor C3. Cleaved C3 on the surface of the microorganism mediates opsonization for clearance, but the impact of MBL on subsequent phagocytosis has not been widely studied. We investigated the role of MBL in complement activation and phagocytosis of various bacteria and yeast species by flow cytometry. We measured both the C3 deposition during serum opsonization of fluorescent-labeled microorganisms as well as subsequent uptake of these microorganisms by human neutrophils. In MBL-deficient sera, a consistently decreased C3 deposition on both zymosan and Candida albicans was found and a reduced phagocytosis by neutrophils that was restored by exogenous MBL. This indicates that the lectin pathway of complement activation is important for the opsonophagocytosis of yeasts. In contrast, the C1q-dependent classical pathway dominated in the opsonization and phagocytosis of Staphylococcus aureus, Streptococcus pneumoniae, and Escherichia coli, whereas no effect of MBL was found. Both the lectin and the classical pathway of complement activation were highly amplified by the alternative route for opsonophagocytosis by neutrophils of yeast as well as microbial species. In summary, our data demonstrate that yeast species are preferentially opsonized and subsequently phagocytosed via activation of the lectin pathway of complement, whereas the uptake of bacterial strains was found to be largely MBL independent.

SummaryWe investigated whether deficiency of mannose-binding lectin (MBL), a component of innate immunity, is associated with neonatal pneumonia and sepsis during the first 72 h, i.e. early onset, and during the first month after birth. In 88 neonatal intensive care patients (71 premature), MBL2 genotype and MBL plasma levels at birth were determined prospectively by Taqman analysis and enzyme-linked immunosorbent assay, respectively. Thirty-five neonates (40%) had low, i.e. Յ 0·7 mg/ml, MBL plasma levels at birth. Median (interquartile range) MBL plasma levels in 32 no early-onset sepsis (EOS) cases, 44 possible EOS cases and 11 EOS cases were 1·57 (0·57-2·67) mg/ml, 1·05 (0·41-1·70) mg/ml and 0·20 (0·10-0·77) mg/ml, respectively (P < 0·01). During the first month, 28 neonates (32%) had no infection, 49 (55%) had suspected infection, five (6%) had pneumonia and six (7%) had culture-proven sepsis. Low MBL levels at birth were associated both with an increased risk of developing pneumonia (OR: 12·0; 95% CI: 1·1-126·1; P = 0·04) and culture-proven sepsis (OR: 15·0; 95% CI: 1·5-151·3; P = 0·02). These results were confirmed by genetic analysis of MBL deficiency. Low MBL levels at birth are associated with an increased risk of early-onset sepsis, culture-proven sepsis and pneumonia during the first month of life.