Abstract
Necrotising enterocolitis (NEC) causes significant morbidity and mortality in premature infants. The role of innate immunity in the pathogenesis of NEC remains unclear. Mannose-binding 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 (<10 ng/mL) to 277 ng/mL. Eighteen of 32 (56%) NEC cases had higher MASP-2 levels (≥30 ng/mL) compared with 22 of 64 (34%) controls (univariate OR 2.46; 95% CI 1.03–5.85; p = 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 = 0.027). MBL levels were not associated with NEC (p = 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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- MASP-2:
-
mannose-binding lectin-associated serine protease-2
- MBL:
-
mannose-binding lectin
- NEC:
-
necrotising enterocolitis
- PDA:
-
perstistent ductus arteriosus
References
Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR, Bauer CR, Donovan EF, Korones SB, Laptook AR, Lemons JA, Oh W, Papile LA, Shankaran S, Stevenson DK, Tyson JE, Poole WK, NICHD Neonatal Research Network 2007 Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol 196: 147. e1–e8
Caplan MS, Simon D, Jilling T 2005 The role of PAF, TLR, and the inflammatory response in neonatal necrotizing enterocolitis. Semin Pediatr Surg 14: 145–151
Lin PW, Stoll BJ 2006 Necrotising enterocolitis. Lancet 368: 1271–1283
Kessler U, Mungnirandr A, Nelle M, Nimmo AF, Zachariou Z, Berger S 2006 A simple presurgical necrotizing enterocolitis-mortality scoring system. J Perinatol 26: 764–768
Strunk T, Richmond P, Simmer K, Currie A, Levy O, Burgner D 2007 Neonatal immune responses to coagulase-negative staphylococci. Curr Opin Infect Dis 20: 370–375
Thiel S 2007 Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins, and associated proteins. Mol Immunol 44: 3875–3888
Sorensen R, Thiel S, Jensenius JC 2005 Mannan-binding-lectin-associated serine proteases, characteristics and disease associations. Springer Semin Immunopathol 27: 299–319
Frakking FN, Brouwer N, van Eijkelenburg NK, Merkus MP, Kuijpers TW, Offringa M, Dolman KM 2007 Low mannose-binding lectin (MBL) levels in neonates with pneumonia and sepsis. Clin Exp Immunol 150: 255–262
de Benedetti F, Auriti C, D'Urbano LE, Ronchetti MP, Rava L, Tozzi A, Ugazio AG, Orzalesi MM 2007 Low serum levels of mannose binding lectin are a risk factor for neonatal sepsis. Pediatr Res 61: 325–328
Stengaard-Pedersen K, Thiel S, Gadjeva M, Moller-Kristensen M, Sorensen R, Jensen LT, Sjoholm AG, Fugger L, Jensenius JC 2003 Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med 349: 554–560
Schlapbach LJ, Aebi C, Otth M, Leibundgut K, Hirt A, Ammann RA 2007 Deficiency of mannose-binding lectin-associated serine protease-2 associated with increased risk of fever and neutropenia in pediatric cancer patients. Pediatr Infect Dis J 26: 989–994
Le Mandat Schultz A, Bonnard A, Barreau F, Aigrain Y, Pierre-Louis C, Berrebi D, Peuchmaur M 2007 Expression of TLR-2, TLR-4, NOD2 and pNF-kappaB in a Neonatal Rat Model of Necrotizing Enterocolitis. PLoS One 2: e1102
Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T 1978 Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 187: 1–7
Kaukola T, Herva R, Perhomaa M, Paakko E, Kingsmore S, Vainionpaa L, Hallman M 2006 Population cohort associating chorioamnionitis, cord inflammatory cytokines and neurologic outcome in very preterm, extremely low birth weight infants. Pediatr Res 59: 478–483
Jacobs S, Hunt R, Tarnow-Mordi W, Inder T, Davis P 2007 Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev CD003311
Sankaran K, Puckett B, Lee DS, Seshia M, Boulton J, Qiu Z, Lee SK 2004 Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units. J Pediatr Gastroenterol Nutr 39: 366–372
Llanos AR, Moss ME, Pinzon MC, Dye T, Sinkin RA, Kendig JW 2002 Epidemiology of neonatal necrotising enterocolitis: a population-based study. Paediatr Perinat Epidemiol 16: 342–349
Herrera C, Holberton J, Davis P 2007 Prolonged versus short course of indomethacin for the treatment of patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev CD003480
Holman RC, Stoll BJ, Clarke MJ, Glass RI 1997 The epidemiology of necrotizing enterocolitis infant mortality in the United States. Am J Public Health 87: 2026–2031
Moller-Kristensen M, Jensenius JC, Jensen L, Thielens N, Rossi V, Arlaud G, Thiel S 2003 Levels of mannan-binding lectin-associated serine protease-2 in healthy individuals. J Immunol Methods 282: 159–167
Olesen HV, Jensenius JC, Steffensen R, Thiel S, Schiotz PO 2006 The mannan-binding lectin pathway and lung disease in cystic fibrosis-dysfunction of mannan-binding lectin-associated serine protease 2 (MASP-2) may be a major modifier. Clin Immunol 121: 324–331
Ytting H, Christensen IJ, Thiel S, Jensenius JC, Nielsen HJ 2005 Serum mannan-binding lectin-associated serine protease 2 levels in colorectal cancer: relation to recurrence and mortality. Clin Cancer Res 11: 1441–1446
Deleted in proof
Walsh MC, Bourcier T, Takahashi K, Shi L, Busche MN, Rother RP, Solomon SD, Ezekowitz RA, Stahl GL 2005 Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol 175: 541–546
Hart ML, Ceonzo KA, Shaffer LA, Takahashi K, Rother RP, Reenstra WR, Buras JA, Stahl GL 2005 Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q. J Immunol 174: 6373–6380
Guo RF, Ward PA 2005 Role of C5a in inflammatory responses. Annu Rev Immunol 23: 821–852
Neu J, Chen M, Beierle E 2005 Intestinal innate immunity: how does it relate to the pathogenesis of necrotizing enterocolitis. Semin Pediatr Surg 14: 137–144
van der Zwet WC, Catsburg A, van Elburg RM, Savelkoul PH, Vandenbroucke-Grauls CM 2008 Mannose-binding lectin (MBL) genotype in relation to risk of nosocomial infection in pre-term neonates in the neonatal intensive care unit. Clin Microbiol Infect 14: 130–135
Ahrens P, Kattner E, Kohler B, Hartel C, Seidenberg J, Segerer H, Moller J, Gopel W 2004 Mutations of genes involved in the innate immune system as predictors of sepsis in very low birth weight infants. Pediatr Res 55: 652–656
Deleted in proof
Aittoniemi J, Miettinen A, Laippala P, Isolauri E, Viikari J, Ruuska T, Soppi E 1996 Age-dependent variation in the serum concentration of mannan-binding protein. Acta Paediatr 85: 906–909
Moonen RM, Paulussen AD, Souren NY, Kessels AG, Rubio-Gozalbo ME, Villamor E 2007 Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis. Pediatr Res 62: 188–190
Henderson G, Craig S, Baier J, Helps N, Brocklehurst P, McGuire W 2007 Cytokine gene polymorphisms in preterm infants with necrotising enterocolitis: genetic association study. Arch Dis Child Fetal Neonatal Ed, in press
Szebeni B, Szekeres R, Rusai K, Vannay A, Veres G, Treszl A, Arato A, Tulassay T, Vasarhelyi B 2006 Genetic polymorphisms of CD14, toll-like receptor 4, and caspase-recruitment domain 15 are not associated with necrotizing enterocolitis in very low birth weight infants. J Pediatr Gastroenterol Nutr 42: 27–31
Acknowledgements
The authors thank Lorenz Risch, M.D., Risch Laboratories, Bern, for providing us with serum samples of healthy term neonates, and Tina Brehmer, Department of Pediatric Surgery, University of Bern, for help in data acquisition.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by a grant of the Rossi Research Fund, Department of Pediatrics, University of Bern, Switzerland.
Rights and permissions
About this article
Cite this article
Schlapbach, L., Aebi, C., Fisch, U. et al. Higher Cord Blood Levels of Mannose-Binding Lectin-Associated Serine Protease-2 in Infants With Necrotising Enterocolitis. Pediatr Res 64, 562–566 (2008). https://doi.org/10.1203/PDR.0b013e3181841335
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e3181841335
This article is cited by
-
Mannose-binding lectin and mannose-binding protein-associated serine protease 2 levels and infection in very-low-birth-weight infants
Pediatric Research (2018)
-
Lectin pathway of complement activation and relation with clinical complications in critically ill children
Pediatric Research (2014)
-
M-ficolin concentrations in cord blood are related to circulating phagocytes and to early-onset sepsis
Pediatric Research (2012)
