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Published in: Intensive Care Medicine 10/2007

01-10-2007 | Pediatric Original

Mannose-binding lectin polymorphisms and pulmonary outcome in premature neonates: a pilot study

Authors: Ettore Capoluongo, Giovanni Vento, Sandro Rocchetti, Emiliano Giardina, Paola Concolino, Cecilia Sinibaldi, Concetta Santonocito, Valentina Vendettuoli, Milena Tana, Chiara Tirone, Cecilia Zuppi, Costantino Romagnoli, Giuseppe Novelli, Bruno Giardina, Franco Ameglio

Published in: Intensive Care Medicine | Issue 10/2007

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Abstract

Objective

Mannose-binding lectin (MBL2) is a collectin molecule able to activate the complement system and the subsequent inflammatory mechanisms. Several MBL2 genetic variants have been described, including the six variants studied in this report, which are those analyzed in most detail in the medical literature.

Design

The present study analyzes the prevalence of MBL2 gene variants in preterm newborns and associates individual genotypes with pulmonary outcome variables. All polymorphisms were analyzed by means of a commercially available reverse dot–blot kit.

Setting

Tertiary neonatal intensive care unit.

Patients and participants

Seventy-five consecutive preterm newborns.

Measurements and results

Two variants were particularly analyzed: –550G > C and R52C. The first one is known to be associated with lower protein synthesis when included in specific haplotypes. The homozygous and heterozygous –550G > C mutations were significantly associated with protective effects regarding different lung outcome variables, including shorter duration of mechanical ventilation, hours of continuous positive airway pressure and lower number of hemotransfusions. In contrast, the heterozygous R52C mutation was associated with unfavorable outcome, including higher bronchopulmonary dysplasia prevalence. Multivariate logistic regression analysis showed that these associations were independent of gestational age and birth weight. In addition, four groups of patients were defined on the basis of haplotype combinations. Those known to be associated with low serum MBL2 levels were linked to a better outcome in terms of factors such as hours of mechanical ventilation, continuous positive airway pressure, number of hemotransfusions and bronchopulmonary disease development.

Conclusions

The four haplotype combination groups may have a potential diagnostic use as opposite risk factors for lung disease of prematurity.
Literature
1.
go back to reference Kilpatrick DC (2002) Mannan-binding lectin and its role in innate immunity. Transfus Med 12:335–352PubMedCrossRef Kilpatrick DC (2002) Mannan-binding lectin and its role in innate immunity. Transfus Med 12:335–352PubMedCrossRef
2.
go back to reference Mullighan CG, Heatley S, Doherty K, Szabo F, Grigg A, Hughes TP, Schwarer AP, Szer J, Tait BD, Bik To L, Bardy PG (2002) Mannose-binding lectin gene polymorphisms are associated with major infection following allergenic hemopoietic stem cell transplantation. Blood 99:3524–3529PubMedCrossRef Mullighan CG, Heatley S, Doherty K, Szabo F, Grigg A, Hughes TP, Schwarer AP, Szer J, Tait BD, Bik To L, Bardy PG (2002) Mannose-binding lectin gene polymorphisms are associated with major infection following allergenic hemopoietic stem cell transplantation. Blood 99:3524–3529PubMedCrossRef
3.
go back to reference Worthley DL, Bardy PG, Mullighan CG (2005) Mannose-binding lectin: biology and clinical implications. Intern Med J 35:548–555PubMedCrossRef Worthley DL, Bardy PG, Mullighan CG (2005) Mannose-binding lectin: biology and clinical implications. Intern Med J 35:548–555PubMedCrossRef
4.
go back to reference Casanova JL, Abel L (2004) Human mannose-binding lectin in immunity: friend, foe, or both? J Exp Med 199:1295–1299PubMedCrossRef Casanova JL, Abel L (2004) Human mannose-binding lectin in immunity: friend, foe, or both? J Exp Med 199:1295–1299PubMedCrossRef
5.
go back to reference Eisen DP, Minchinton RM (2003) Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 37:1496–1505PubMedCrossRef Eisen DP, Minchinton RM (2003) Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 37:1496–1505PubMedCrossRef
6.
go back to reference Ip WK, To YF, Cheng SK, Lau YL (2004) Serum mannose-binding lectin levels and mbl2 gene polymorphisms in different age and gender groups of southern Chinese adults. Scand J Immunol 59:310–314PubMedCrossRef Ip WK, To YF, Cheng SK, Lau YL (2004) Serum mannose-binding lectin levels and mbl2 gene polymorphisms in different age and gender groups of southern Chinese adults. Scand J Immunol 59:310–314PubMedCrossRef
7.
go back to reference Verdu P, Barreiro LB, Patin E, Gessain A, Cassar O, Kidd JR, Kidd KK, Behar DM, Froment A, Heyer E, Sica L, Casanova JL, Abel L, Quintana-Murci L (2006) Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles. Hum Mol Genet 15:2650–2658PubMedCrossRef Verdu P, Barreiro LB, Patin E, Gessain A, Cassar O, Kidd JR, Kidd KK, Behar DM, Froment A, Heyer E, Sica L, Casanova JL, Abel L, Quintana-Murci L (2006) Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles. Hum Mol Genet 15:2650–2658PubMedCrossRef
8.
go back to reference Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163:1723–1729PubMed Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163:1723–1729PubMed
9.
go back to reference Capoluongo E, Vento G, Ameglio F, Lulli P, Matassa PG, Carrozza C, Santini SA, Antenucci M, Castagnola M, Giardina B, Romagnoli C, Zuppi C (2006) Increased levels of IGF-1 and beta2-microglobulin in epithelial lining fluid of preterm newborns developing chronic lung disease. effects of rhG-CSF. Int J Immunopathol Pharmacol 19:57–66PubMed Capoluongo E, Vento G, Ameglio F, Lulli P, Matassa PG, Carrozza C, Santini SA, Antenucci M, Castagnola M, Giardina B, Romagnoli C, Zuppi C (2006) Increased levels of IGF-1 and beta2-microglobulin in epithelial lining fluid of preterm newborns developing chronic lung disease. effects of rhG-CSF. Int J Immunopathol Pharmacol 19:57–66PubMed
10.
go back to reference Vento G, Capoluongo E, Matassa PG, Concolino P, Vendettuoli V, Vaccarella C, Frezza S, Zuppi C, Romagnoli C, Ameglio F (2006) Serum levels of seven cytokines in premature ventilated newborns: correlations with old and new forms of bronchopulmonary dysplasia. Intensive Care Med 32:723–730PubMedCrossRef Vento G, Capoluongo E, Matassa PG, Concolino P, Vendettuoli V, Vaccarella C, Frezza S, Zuppi C, Romagnoli C, Ameglio F (2006) Serum levels of seven cytokines in premature ventilated newborns: correlations with old and new forms of bronchopulmonary dysplasia. Intensive Care Med 32:723–730PubMedCrossRef
11.
go back to reference Capoluongo E, Concolino P, Giardina B, Zuppi C, Ameglio F, Vento G, Romagnoli C (2006) Is there a relationship between ELF free-IGF-1 levels and fibrotic process enhancement characterizing CLD development in neutropenic premature babies? Pediatr Pulmonol 41:286–287PubMedCrossRef Capoluongo E, Concolino P, Giardina B, Zuppi C, Ameglio F, Vento G, Romagnoli C (2006) Is there a relationship between ELF free-IGF-1 levels and fibrotic process enhancement characterizing CLD development in neutropenic premature babies? Pediatr Pulmonol 41:286–287PubMedCrossRef
12.
go back to reference Capoluongo E, Vento G, Santonocito C, Matassa PG, Vaccarella C, Giardina B, Romagnoli C, Zuppi C, Ameglio F (2005) Comparison of serum levels of seven cytokines in premature newborns undergoing different ventilatory procedures: high frequency oscillatory ventilation or synchronized intermittent mandatory ventilation. Eur Cytokine Netw 16:199–205PubMed Capoluongo E, Vento G, Santonocito C, Matassa PG, Vaccarella C, Giardina B, Romagnoli C, Zuppi C, Ameglio F (2005) Comparison of serum levels of seven cytokines in premature newborns undergoing different ventilatory procedures: high frequency oscillatory ventilation or synchronized intermittent mandatory ventilation. Eur Cytokine Netw 16:199–205PubMed
13.
go back to reference Vento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive Care Med 31:463–470PubMedCrossRef Vento G, Matassa PG, Ameglio F, Capoluongo E, Zecca E, Tortorolo L, Martelli M, Romagnoli C (2005) HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial. Intensive Care Med 31:463–470PubMedCrossRef
14.
go back to reference Capoluongo E, Ameglio F, Lulli P, Minucci A, Santonocito C, Concolino P, Di Stasio E, Boccacci S, Vendettuoli V, Giuratrabocchetta G, De Cunto A, Tana M, Romagnoli C, Zuppi C, Vento G (2007) Epithelial lining fluid free IGF-1/PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants. Am J Physiol Endocrinol Metab 292:E308–313PubMedCrossRef Capoluongo E, Ameglio F, Lulli P, Minucci A, Santonocito C, Concolino P, Di Stasio E, Boccacci S, Vendettuoli V, Giuratrabocchetta G, De Cunto A, Tana M, Romagnoli C, Zuppi C, Vento G (2007) Epithelial lining fluid free IGF-1/PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants. Am J Physiol Endocrinol Metab 292:E308–313PubMedCrossRef
15.
go back to reference Davies PL, Maxwell NC, Kotecha S (2006) The role of inflammation and infection in the development of chronic lung disease of prematurity. Adv Exp Med Biol 582:101–110PubMedCrossRef Davies PL, Maxwell NC, Kotecha S (2006) The role of inflammation and infection in the development of chronic lung disease of prematurity. Adv Exp Med Biol 582:101–110PubMedCrossRef
16.
go back to reference Annells MF, Hart PH, Mullighan CG, Heatley SL, Robinson JS, Bardy P, McDonald HM (2004) Interleukins-1, -4, -6, -10, tumor necrosis factor, transforming growth factor-beta, FAS, and mannose-binding protein C gene polymorphisms in Australian women: Risk of preterm birth. Am J Obstet Gynecol 191:2056–2067PubMedCrossRef Annells MF, Hart PH, Mullighan CG, Heatley SL, Robinson JS, Bardy P, McDonald HM (2004) Interleukins-1, -4, -6, -10, tumor necrosis factor, transforming growth factor-beta, FAS, and mannose-binding protein C gene polymorphisms in Australian women: Risk of preterm birth. Am J Obstet Gynecol 191:2056–2067PubMedCrossRef
17.
go back to reference Crosdale DJ, Ollier WE, Thomson W, Dyer PA, Jensenious J, Johnson RW, Poulton KV (2000) Mannose binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids. Eur J Immunogenet 27:111–117PubMedCrossRef Crosdale DJ, Ollier WE, Thomson W, Dyer PA, Jensenious J, Johnson RW, Poulton KV (2000) Mannose binding lectin (MBL) genotype distributions with relation to serum levels in UK Caucasoids. Eur J Immunogenet 27:111–117PubMedCrossRef
18.
go back to reference Davies JC, Turner MW, Klein N. London MBL CF Study Group (2004). Impaired pulmonary status in cystic fibrosis adults with two mutated MBL-2 alleles. Eur Respir J 24:798–804PubMedCrossRef Davies JC, Turner MW, Klein N. London MBL CF Study Group (2004). Impaired pulmonary status in cystic fibrosis adults with two mutated MBL-2 alleles. Eur Respir J 24:798–804PubMedCrossRef
19.
go back to reference Aittoniemi J, Soranummi H, Rovio AT, Hurme M, Pessi T, Nieminen M, Karjalainen J (2005) Mannose-binding lectin 2 (MBL2) gene polymorphism in asthma and atopy among adults. Clin Exp Immunol 142:120–124PubMedCrossRef Aittoniemi J, Soranummi H, Rovio AT, Hurme M, Pessi T, Nieminen M, Karjalainen J (2005) Mannose-binding lectin 2 (MBL2) gene polymorphism in asthma and atopy among adults. Clin Exp Immunol 142:120–124PubMedCrossRef
20.
go back to reference Frakking FN, Brouwer N, Zweers D, Merkus MP, Kuijpers TW, Offringa M, Dolman KM (2006) High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates. Clin Exp Immunol 145:5–12PubMedCrossRef Frakking FN, Brouwer N, Zweers D, Merkus MP, Kuijpers TW, Offringa M, Dolman KM (2006) High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates. Clin Exp Immunol 145:5–12PubMedCrossRef
21.
go back to reference Henderson-Smart DJ, Hutchinson JL, Donoghue DA, Evans NJ, Simpson JM, Wright I (2006) Australian and New Zealand Neonatal Network. Prenatal predictors of chronic lung disease in very preterm infants. Arch Dis Child Fetal Neonatal Ed 91:F40–45PubMedCrossRef Henderson-Smart DJ, Hutchinson JL, Donoghue DA, Evans NJ, Simpson JM, Wright I (2006) Australian and New Zealand Neonatal Network. Prenatal predictors of chronic lung disease in very preterm infants. Arch Dis Child Fetal Neonatal Ed 91:F40–45PubMedCrossRef
22.
go back to reference Ameglio F, Vento G, Romagnoli C, Giardina B, Capoluongo E (2007) Association of MBL2 variants with early preterm delivery. Genet Med 9:136–137PubMedCrossRef Ameglio F, Vento G, Romagnoli C, Giardina B, Capoluongo E (2007) Association of MBL2 variants with early preterm delivery. Genet Med 9:136–137PubMedCrossRef
23.
go back to reference Bodamer OA, Mitterer G, Maurer W, Pollak A, Mueller MW, Schmidt WM (2006) Evidence for an association between mannose-binding lectin 2 (MBL2) gene polymorphisms and pre-term birth. Genet Med 8:518–524PubMed Bodamer OA, Mitterer G, Maurer W, Pollak A, Mueller MW, Schmidt WM (2006) Evidence for an association between mannose-binding lectin 2 (MBL2) gene polymorphisms and pre-term birth. Genet Med 8:518–524PubMed
24.
go back to reference Vento G, Matassa PG, Capoluongo E, Tortorolo L, Romagnoli C, Ameglio F, Lassus P, Andersson S (2003) Glucocorticoids in preterm infants and discrepancies of vascular endothelial growth factor. Am J Respir Crit Care Med 168:501–502PubMed Vento G, Matassa PG, Capoluongo E, Tortorolo L, Romagnoli C, Ameglio F, Lassus P, Andersson S (2003) Glucocorticoids in preterm infants and discrepancies of vascular endothelial growth factor. Am J Respir Crit Care Med 168:501–502PubMed
25.
go back to reference Coalson JJ, Gerstmann DR, Winter VT, Delemos RA (1991) Bacterial colonization and infection studies in the premature baboon with bronchopulmonary dysplasia. Am Rev Respir Dis 144:1140–1146PubMed Coalson JJ, Gerstmann DR, Winter VT, Delemos RA (1991) Bacterial colonization and infection studies in the premature baboon with bronchopulmonary dysplasia. Am Rev Respir Dis 144:1140–1146PubMed
Metadata
Title
Mannose-binding lectin polymorphisms and pulmonary outcome in premature neonates: a pilot study
Authors
Ettore Capoluongo
Giovanni Vento
Sandro Rocchetti
Emiliano Giardina
Paola Concolino
Cecilia Sinibaldi
Concetta Santonocito
Valentina Vendettuoli
Milena Tana
Chiara Tirone
Cecilia Zuppi
Costantino Romagnoli
Giuseppe Novelli
Bruno Giardina
Franco Ameglio
Publication date
01-10-2007
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 10/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0793-x

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