nach oben

Erschienen in:

01.10.2007 | Pediatric Original

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

verfasst von: 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

Erschienen in: Intensive Care Medicine | Ausgabe 10/2007

Einloggen, um Zugang zu erhalten

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.

Kilpatrick DC (2002) Mannan-binding lectin and its role in innate immunity. Transfus Med 12:335–352PubMedCrossRef

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

Worthley DL, Bardy PG, Mullighan CG (2005) Mannose-binding lectin: biology and clinical implications. Intern Med J 35:548–555PubMedCrossRef

Casanova JL, Abel L (2004) Human mannose-binding lectin in immunity: friend, foe, or both? J Exp Med 199:1295–1299PubMedCrossRef

Eisen DP, Minchinton RM (2003) Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 37:1496–1505PubMedCrossRef

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

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

Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163:1723–1729PubMed

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

Titel: Mannose-binding lectin polymorphisms and pulmonary outcome in premature neonates: a pilot study
verfasst von: 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
Publikationsdatum: 01.10.2007
Verlag: Springer-Verlag
Erschienen in: Intensive Care Medicine / Ausgabe 10/2007
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-007-0793-x

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

hier abonnieren

Springer Medizin

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