Subscribe to RSS
DOI: 10.1055/s-0038-1675801
Use of Mannose-Binding Lectin Gene Polymorphisms and the Serum MBL Level for the Early Detection of Neonatal Sepsis
Publication History
06 August 2018
25 October 2018
Publication Date:
09 November 2018 (online)
Abstract
Background Mannose-binding lectin (MBL) is a component of innate immunity and is particularly important in neonates, in whom adaptive immunity has not yet completely developed. MBL deficiency and MBL2 gene polymorphisms are associated with an opsonization defect and have been associated with neonatal sepsis.
Aim The aim of our study was to assess serum MBL levels and genotype MBL2 genes to determine whether they can serve as markers for predicting neonatal sepsis in neonatal intensive care units.
Patients and Methods A case-control study was conducted with 114 neonates classified into two groups: the septic group included 64 neonates (41 preterm and 23 full-term infants), and the non-septic control group included 50 neonates (29 preterm and 21 full-term infants). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was used to genotype MBL2 gene exon 1 (rs1800450) and (rs1800451) SNPs. Enzyme-linked immunosorbent assay (ELISA) was used to measure MBL serum concentrations.
Results The polymorphic genotypes BB and AC at codons 54 and 57, respectively, showed higher frequencies than the wild-type genotype (AA) (14.1% versus 12.9% and 28.1% versus 19.4% respectively) in both groups, and this difference was greater in the septic group than in the non-septic group; however, the differences did not reach statistical significance. The B and C allele frequencies were also higher in the septic group than in the non-septic group, but the differences did not reach statistical significance (p = 0.282 and 0.394, respectively). The serum levels of MBL were significantly lower in the septic group than in the non-septic group (p = 0.028).
Conclusion This study found no association between MBL levels or MBL2 exon 1 genotypes or alleles and neonatal sepsis risk. Further studies with larger sample sizes are needed to determine the role of the MBL2 gene as a risk factor and early predictor of neonatal sepsis.
-
References
- 1 Shah BA, Padbury JF. Neonatal sepsis: an old problem with new insights. Virulence 2014; 5 (01) 170-178
- 2 Hornik CP, Fort P, Clark RH. , et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev 2012; 88 (Suppl. 02) S69-S74
- 3 Kellogg JA, Ferrentino FL, Goodstein MH, Liss J, Shapiro SL, Bankert DA. Frequency of low level bacteremia in infants from birth to two months of age. Pediatr Infect Dis J 1997; 16 (04) 381-385
- 4 Mitha A, Foix-L'Hélias L, Arnaud C. , et al; EPIPAGE Study Group. Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants. Pediatrics 2013; 132 (02) e372-e380
- 5 Takahashi K, Ip WE, Michelow IC, Ezekowitz RAB. The mannose-binding lectin: a prototypic pattern recognition molecule. Curr Opin Immunol 2006; 18 (01) 16-23
- 6 Wagner TA, Gravett CA, Healy S. , et al. Emerging biomarkers for the diagnosis of severe neonatal infections applicable to low resource settings. J Glob Health 2011; 1 (02) 210-223
- 7 Zhang AQ, Yue CL, Pan W. , et al. Mannose-binding lectin polymorphisms and the risk of sepsis: evidence from a meta-analysis. Epidemiol Infect 2014; 142 (10) 2195-2206
- 8 Gordon AC, Waheed U, Hansen TK. , et al. Mannose-binding lectin polymorphisms in severe sepsis: relationship to levels, incidence, and outcome. Shock 2006; 25 (01) 88-93
- 9 Seyfarth J, Garred P, Madsen HO. The ‘involution’ of mannose-binding lectin. Hum Mol Genet 2005; 14 (19) 2859-2869
- 10 Eisen DP, Minchinton RM. Impact of mannose-binding lectin on susceptibility to infectious diseases. Clin Infect Dis 2003; 37 (11) 1496-1505
- 11 Presanis JS, Kojima M, Sim RB. Biochemistry and genetics of mannan-binding lectin (MBL). Biochem Soc Trans 2003; 31 (Pt 4): 748-752
- 12 Turner MW, Hamvas RM. Mannose-binding lectin: structure, function, genetics and disease associations. Rev Immunogenet 2000; 2 (03) 305-322
- 13 Garred P. Mannose-binding lectin genetics: from A to Z. Biochem Soc Trans 2008; 36 (Pt 6): 1461-1466
- 14 Bouwman LH, Roep BO, Roos A. Mannose-binding lectin: clinical implications for infection, transplantation, and autoimmunity. Hum Immunol 2006; 67 (4-5): 247-256
- 15 Pascale G, Cutuli SL, Pennisi MA, Antonelli M. The role of mannose-binding lectin in severe sepsis and septic shock. Mediators of inflammation. 2013. http://dx.doi.org/10.1155/2013/625803
- 16 Levy MM, Artigas A, Phillips GS. , et al. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis 2012; 12 (12) 919-924
- 17 Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr 1988; 112 (05) 761-767
- 18 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16 (03) 1215
- 19 Frakking FN, Brouwer N, Zweers D. , et al. High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates. Clin Exp Immunol 2006; 145 (01) 5-12
- 20 Auriti C, Prencipe G, Inglese R. , et al. Role of mannose-binding lectin in nosocomial sepsis in critically ill neonates. Hum Immunol 2010; 71 (11) 1084-1088
- 21 El-Shimi MS, Khafagy SM, Abdel-al H, Omara MA. Mannose-binding lectin deficiency in preterm neonates. Egypt J Pediatr Allergy Immunol 2010; 8 (02) 75-80
- 22 Ozdemir O, Dinleyici EC, Tekin N, Colak O, Aksit MA. Low-mannose-binding lectin levels in susceptibility to neonatal sepsis in preterm neonates with fetal inflammatory response syndrome. J Matern Fetal Neonatal Med 2010; 23 (09) 1009-1013
- 23 de Benedetti F, Auriti C, D'Urbano LE. , et al. Low serum levels of mannose binding lectin are a risk factor for neonatal sepsis. Pediatr Res 2007; 61 (03) 325-328
- 24 Wahab Mohamed WA, Saeed MA. Mannose-binding lectin serum levels in neonatal sepsis and septic shock. J Matern Fetal Neonatal Med 2012; 25 (04) 411-414
- 25 Xue H, Xue X, Yang C, Chen O, Lin N, Lin Y, Chen M, Rao D, Lin H. Low Serum Mannose Binding Lectin (MBL) Levels and -221 YX Genotype of MBL2 Gene Are Susceptible to Neonatal Sepsis in the Chinese Han Population. 2017; 27 (03) 9448
- 26 Klostergaard A, Steffensen R, Møller JK, Peterslund N, Juhl-Christensen C, Mølle I. Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: no impact of chitotriosidase and mannose-binding lectin polymorphisms. Eur J Haematol 2010; 85 (01) 58-64
- 27 Huh JW, Song K, Yum JS, Hong SB, Lim CM, Koh Y. Association of mannose-binding lectin-2 genotype and serum levels with prognosis of sepsis. Crit Care 2009; 13 (06) R176
- 28 Koroglu OA, Onay H, Erdemir G. , et al. Mannose-binding lectin gene polymorphism and early neonatal outcome in preterm infants. Neonatology 2010; 98 (04) 305-312
- 29 Özkan H, Köksal N, Çetinkaya M. , et al. Serum mannose-binding lectin (MBL) gene polymorphism and low MBL levels are associated with neonatal sepsis and pneumonia. J Perinatol 2012; 32 (03) 210-217
- 30 Larsen F, Madsen HO, Sim RB, Koch C, Garred P. Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein. J Biol Chem 2004; 279 (20) 21302-21311
- 31 Sumiya M, Super M, Tabona P. , et al. Molecular basis of opsonic defect in immunodeficient children. Lancet 1991; 337 (8757): 1569-1570
- 32 Terai I, Kobayashi K, Matsushita M, Miyakawa H, Mafune N, Kikuta H. Relationship between gene polymorphisms of mannose-binding lectin (MBL) and two molecular forms of MBL. Eur J Immunol 2003; 33 (10) 2755-2763
- 33 Lin CL, Siu LK, Lin JC. , et al. Mannose-binding lectin gene polymorphism contributes to recurrence of infective exacerbation in patients with COPD. Chest 2011; 139 (01) 43-51
- 34 Chalmers JD, McHugh BJ, Doherty C. , et al. Mannose-binding lectin deficiency and disease severity in non-cystic fibrosis bronchiectasis: a prospective study. Lancet Respir Med 2013; 1 (03) 224-232