Higher Cord Blood Levels of Mannose-Binding Lectin-Associated Serine Protease-2 in Infants With Necrotising Enterocolitis

Abstract

Necrotising enterocolitis (NEC) causes significant morbidity and mortality in premature infants. The role of innate immunity in the pathogenesis of NEC remains unclear. Mannosebinding lectin (MBL) recognizes microorganisms and activates the complement system via MBL-associated serine protease-2 (MASP-2). The aim of this study was to investigate whether MBL and MASP-2 are associated with NEC. This observational case-control study included 32 infants with radiologically confirmed NEC and 64 controls. MBL and MASP-2 were measured in cord blood using ELISA. Multivariate logistic regression was performed. Of the 32 NEC cases (median gestational age, 30.5 wk), 13 (41%) were operated and 5 (16%) died. MASP-2 cord blood concentration ranged from undetectable (Ͻ10 ng/mL) to 277 ng/mL. Eighteen of 32 (56%) NEC cases had higher MASP-2 levels (Ն30 ng/mL) compared with 22 of 64 (34%) controls (univariate OR 2.46; 95% CI 1.03-5.85; p ϭ 0.043). Higher cord blood MASP-2 levels were significantly associated with an increased risk of NEC in multivariate analysis (OR 3.00; 95% CI 1.17-7.93; p ϭ 0.027). MBL levels were not associated with NEC (p ϭ 0.64). In conclusion, infants later developing NEC had significantly higher MASP-2 cord blood levels compared with controls. Higher MASP-2 may favor complement-mediated inflammation and could thereby predispose to NEC. A lthough prognosis for premature infants has improved over the last years as a result of advances in perinatal and intensive care, morbidity and mortality due to necrotising enterocolitis (NEC) remain high (1). Numerous risk factors, including prematurity, intrauterine growth retardation, formula feeding, bacterial infection, and intestinal ischemia have been implicated in the pathogenesis of the disease (2,3). However, since the exact pathophysiological mechanisms remain undefined, identification of infants at risk for NEC and early recognition of NEC represent a challenge (4).Early infancy is a vulnerable period of transition from passive, transplacentally acquired immunity to individual, adaptive immunity. Since premature infants experience both humoral and cellular immunodeficiency, they rely on genetically determined innate defense mechanisms (5). Innate immunity is mainly mediated by host proteins that recognize conserved pathogen-associated molecular patterns, such as repetitive sugar arrays present on many microorganisms but not on mammalian cells (6). The lectin pathway of complement activation represents an important component of innate immunity and consists of Mannose-binding lectin (MBL) and L-and H-ficolins, which recognize various microorganisms (6). Both MBL and ficolins rely on MBL-associated serine protease-2 (MASP-2) to activate the complement system (6). Upon binding of MBL/MASP-2 complexes to microbial surfaces, MASP-2 sequentially cleaves C4 and C2, thereby generating the C3 convertase C4bC2b, which finally leads to opsonization and lysis of pathogens and recruitment of inflammatory cells (7).Due to single nucleotide polymorphisms within the ...

Lectin pathway of complement activation and relation with clinical complications in critically ill children

“…Thus, critical illness has an acute effect on most of these proteins. Matching for age appeared crucial because of the important changes with age reported for most of these proteins (10,(15)(16)(17)(18) and largely confirmed in our cohorts of healthy and critically ill children.…”

“…Low MBL levels in blood from neonates were related to an increased risk of neonatal sepsis and pneumonia (24,25). Cord blood MASP-2 levels tended to be higher for babies with infections (26) and were higher for neonates who developed NEC (17). Risk of death and need for mechanical ventilation for neonates with NEC were higher when M-ficolin levels were low (10).…”

M-ficolin concentrations in cord blood are related to circulating phagocytes and to early-onset sepsis

“…M-ficolin cord blood concentration increased with gestational age, although less as compared with the hepatically synthesized lectin pathway components (5,18). We have previously described an increase of M-ficolin over the first year of life in a cohort including controls from this study (19).…”

Multiplex sequence-specific polymerase chain reaction reveals new MASP2 haplotypes associated with MASP-2 and MAp19 serum levels

“…Levels above 450 ng/mL were reported to be associated with cancer recurrence and poor postoperative survival of colorectal cancer patients [48], as well as with Crohn's disease [49]. Levels higher than 300 ng/mL were also associated with significant morbidity and mortality in premature infants with necrotizing enterocolitis [50]. Thus, MASP-2 might have a dual role in susceptibility to disease, similar to MBL [51].…”