Development of functional mannose binding lectin is delayed in extremely low birth weight infants

Abstract

Abstract Background Mannose binding lectin (MBL) is a liver derived plasma pattern recognition molecule that plays an important role in innate immune defence. Genetically driven deficiencies in MBL level and function are associated with increased frequency and severity of infection, and increased prevalence of autoimmune and chronic inflammatory diseases. Extremely low birth weight infants (ELBWI) are at increased risk of acquiring infection and innate immunity is particularly important in this group. We assessed functional MBL level and capacity to activate the complement cascade in ELBWI. Methods ELBW infants (< 1500 g, n=141) were recruited from the Mater Mothers’ Hospital (informed parental consent, ethics #492M). Whole blood was collected into EDTA coated tubes at birth (cord blood), and at D7 and D28 postpartum (heel prick). Functional MBL level and C4 deposition capacity were determined by ELISAs. MBL genotype was determined by PCR. MBL oligomerisation was determined by western blot. Full birth weight infants (n=190) and healthy adult blood donors (n=236) were used as comparators (unpaired t-test P<0.05). Results Compared to both full term neonates and adults, new born ELBW infants had significantly reduced MBL level (both P<0.001) and C4 deposition capacity (both P<0.001). Mannan binding and C4 deposition capacity of MBL in ELBW neonates increased over the first 28 Days, reaching comparative function to full term neonates by D7. Increased mannan binding and C4 deposition was associated with increased oligomerisation of MBL. Conclusions Development of functional MBL was delayed in ELBW infants. MBL oligomerisation was associated with increased capacity to activate the complement cascade.