Use of Mannose-Binding Lectin Gene Polymorphisms and the Serum MBL Level for the Early Detection of Neonatal Sepsis

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.

Role of MBL2 Polymorphisms in Sepsis and Survival: A Pilot Study and In Silico Analysis

“…The genotype frequencies of the SNPs in our study were in agreement with previous published data among the Egyptian population; the genotype frequency of rs1800451 was similar to the frequency found by Badawy and colleagues in Egyptian population [ 23 ], as well as those from studies in other populations [ 14 , 37 ]. The genotype frequency results of rs1800450 were very similar to that found by Nasr et al in a recent study in an Egyptian population, with frequencies of 41.7%, 58.3%, 0.0% for the AA, AB and BB genotypes, respectively [ 38 ], similar to the results found by Badawy and colleagues [ 23 ]. The notable high frequency associated with these variants was observed previously, and attracted much attention, leading to many different hypotheses and an resolved debate concerning the real roles of these variants [ 18 , 19 , 39 , 40 ].…”

“…Moreover, a prospective Dutch study found no association between MBL2 genotypes and the susceptibility to CAP and that MBL2 genotypes could not be considered as factors with major risk for developing infection with CAP [ 49 ]. In addition, regarding neonatal sepsis in an Egyptian population, although an Egyptian cross sectional study found a prevalence of mutant allele B with neonatal sepsis that might indicate a possible role of allele B of codon 54 in neonatal sepsis [ 50 ], another case-controlled study with a larger sample size was conducted on neonates in an Egyptian population and found no association of MBL2 SNPs with sepsis risk [ 23 ].…”

“…Meanwhile, MBL studies have found an astonishing high level of mutations in codon 54 and codon 57 in many populations, which lead to many hypotheses and much debate about the real role of these mutations and pushed for more investigation into their implications for infectious diseases [ 18 , 19 ]. Therefore, many studies investigated the association of exon 1 polymorphisms with the risk of infectious diseases and sepsis, and gave conflicting results [ 14 , 20 , 21 , 22 , 23 ]. These conflicted results indicated the need to further investigate, to identify whether single-nucleotide polymorphisms (SNPs) in this significantly important gene could be used for predicting a defect in our immunity towards infection and sepsis.…”

Mannose-binding lectin serum levels and (Gly54asp) gene polymorphism in recurrent aphthous stomatitis: A case-control study

“…40 Our study revealed that the B allele was expressed in significantly higher percentages of RAS patients (42.5%) than controls (16.3%). In contrast, no significant association could be detected between the MBL2 codon 54 genotypes and severe chronic periodontitis 41 , neonatal sepsis, 42 and recurrent respiratory tract infection in children. 43 Among the 40 RAS patients in our study, 29 (72.5%) had minor ulcers, 8 (20.0%) patients had major ulcers, and 3 (7.5%) patients had herpetiform ulcers.…”

A narrative review of precision medicine in neonatal sepsis: genetic and epigenetic factors associated with disease susceptibility

“…Cumulative evidence confirmed that a low serum MBL concentration resulting from O was associated with a higher incidence of sepsis in all age groups (20,26,(42)(43)(44)(45)(46). Unfortunately, this theory did not hold in observations focused on neonatal sepsis, in which no such correlation was found (18,21,24,25,(47)(48)(49). The mixed data mentioned above raise the question as to the exact role of MBL2 in neonatal sepsis.…”