Low mannose-binding lectin function is associated with sepsis in adult patients (original) (raw)
Related papers
Shock, 2006
Mannose-binding lectin (MBL) genetic polymorphisms result in deficiency of the encoded protein and increased susceptibility to infection, especially in children and the immunocompromised. The objective of this study was to investigate the relationship between MBL-2 exon 1 and promoter 2221 polymorphisms, plasma levels of the encoded protein, and the incidence and outcome of severe sepsis and septic shock. One hundred seventy-four white adult patients with severe sepsis or septic shock were recruited in a prospective multicenter study across eight intensive care units in the South of England, UK. Genotype and haplotype frequencies were compared between normal population controls and patients, and between survivors and nonsurvivors. Plasma levels of encoded protein were related to genotype and outcome. The exon 1 polymorphisms (A/O or O/O) were significantly more common in the patients with severe sepsis and septic shock than in normal healthy adults (54.6% vs. 39.7%, P = 0.001), and there was a significant difference in haplotype frequency between controls and septic patients (P < 0.0001). There was no significant difference in MBL-2 genotype or haplotype frequency between survivors and nonsurvivors. There was a strong relationship between MBL-2 haplotype and plasma MBL concentration (P < 0.001). Individual plasma levels were variable and increased between days 1 and 7. The mortality rate was higher in those with MBL levels <1000 mg/L than in those patients with levels >1000 mg/L (47.2 vs. 22.2%, P = 0.05). We conclude that genetic polymorphisms resulting in mannose-binding lectin deficiency are associated with increased susceptibility to sepsis. The close relationship between polymorphic variants and plasma MBL concentration persists during sepsis but individual levels vary widely. Lower circulating MBL levels are associated with a poor outcome.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015
Sepsis is an increasingly common condition, which continues to be associated with unacceptably high mortality. A large number of association studies have investigated susceptibility to, or mortality from sepsis for variants in the functionally important immune-related gene MBL2. These studies have largely been underpowered and contradictory. We genotyped and analysed four important MBL2 SNPs (rs5030737, rs1800450, rs1800451 and rs7096206) in 1839 European community-acquired pneumonia (CAP) and peritonitis sepsis cases, and 477 controls from the UK. We analysed the following predefined subgroups and outcomes: 28-day and 6 month mortality from sepsis due to CAP or peritonitis combined, 28-day mortality from CAP sepsis, peritonitis sepsis, pneumococcal sepsis or sepsis in younger patients, and susceptibility to CAP sepsis or pneumococcal sepsis in the UK. There were no significant associations (all p-values were greater than 0.05 after correction for multiple testing) between MBL2 g...
Low Serum Levels of Mannose Binding Lectin Are a Risk Factor for Neonatal Sepsis
Pediatric Research, 2007
We investigated the association of mannose-binding lectin (MBL) serum levels with nosocomial sepsis (NS), their changes overtime during infection, their relation with pathogens, with the MBL2 genotype and their relationship with mortality. In a prospective observational study, we included 365 critically ill neonates: 261 had no infection and 104 had at least 1 septic event. The median MBL serum concentration was significantly lower in infected than in noninfected neonates (p Ͻ 0.001). Low MBL levels on admission increased the risk of infection, independently from gestational age and invasive procedures. The median peak MBL level during infection was higher than the median level on admission (p Ͻ 0.001) and was correlated with it (r 2 ϭ 0.83, p Ͻ 0.001). Moreover, MBL levels on admission were not associated with death (OR ϭ 0.80, 95% CI ϭ 0.56 -1.14, p ϭ 0.21). Similarly, no association was found between MBL peak levels during infection and death among infected neonates (OR ϭ 1.10, 95% CI ϭ 0.78 -1.57, p ϭ 0.57). In 127 neonates (42 infected) genotyped for exon-1 and -221 promoter MBL2 variants, we did not find significant difference in the frequencies of MBL2 genotypes between infected and noninfected neonates. Moreover, no association was found between MBL2 genotypes and death. ᭧
Role of mannose-binding lectin in nosocomial sepsis in critically ill neonates
Human Immunology, 2010
We investigated the association of mannose-binding lectin (MBL) serum levels with nosocomial sepsis (NS), their changes overtime during infection, their relation with pathogens, with the MBL2 genotype and their relationship with mortality. In a prospective observational study, we included 365 critically ill neonates: 261 had no infection and 104 had at least 1 septic event. The median MBL serum concentration was significantly lower in infected than in noninfected neonates (p Ͻ 0.001). Low MBL levels on admission increased the risk of infection, independently from gestational age and invasive procedures. The median peak MBL level during infection was higher than the median level on admission (p Ͻ 0.001) and was correlated with it (r 2 ϭ 0.83, p Ͻ 0.001). Moreover, MBL levels on admission were not associated with death (OR ϭ 0.80, 95% CI ϭ 0.56 -1.14, p ϭ 0.21). Similarly, no association was found between MBL peak levels during infection and death among infected neonates (OR ϭ 1.10, 95% CI ϭ 0.78 -1.57, p ϭ 0.57). In 127 neonates (42 infected) genotyped for exon-1 and -221 promoter MBL2 variants, we did not find significant difference in the frequencies of MBL2 genotypes between infected and noninfected neonates. Moreover, no association was found between MBL2 genotypes and death. ᭧
Low mannose-binding lectin (MBL) levels in neonates with pneumonia and sepsis
Clinical & Experimental Immunology, 2007
Summary We investigated whether deficiency of mannose-binding lectin (MBL), a component of innate immunity, is associated with neonatal pneumonia and sepsis during the first 72 h, i.e. early onset, and during the first month after birth. In 88 neonatal intensive care patients (71 premature), MBL2 genotype and MBL plasma levels at birth were determined prospectively by Taqman analysis and enzyme-linked immunosorbent assay, respectively. Thirty-five neonates (40%) had low, i.e. ≤ 0·7 µg/ml, MBL plasma levels at birth. Median (interquartile range) MBL plasma levels in 32 no early-onset sepsis (EOS) cases, 44 possible EOS cases and 11 EOS cases were 1·57 (0·57–2·67) µg/ml, 1·05 (0·41–1·70) µg/ml and 0·20 (0·10–0·77) µg/ml, respectively (P < 0·01). During the first month, 28 neonates (32%) had no infection, 49 (55%) had suspected infection, five (6%) had pneumonia and six (7%) had culture-proven sepsis. Low MBL levels at birth were associated both with an increased risk of developing ...
Pediatric Research, 2014
Background: Critically ill children are susceptible to nosocomial infections, which contribute to adverse outcomes. Deficiencies in the innate immunity lectin pathway of complement activation are implicated in a child's vulnerability to infections in conditions such as cancer, but the role during critical illness remains unclear. We hypothesized that low on-admission levels of the pathway proteins are, in part, genetically determined and associated with susceptibility to infectious complications and adverse outcomes. Methods: We studied protein levels of mannose-binding lectin (MBL), H-ficolin and M-ficolin, three MBL-associatedserine proteases (MASPs) and MBL-associated protein (MAp44), and relation with functional genetic polymorphisms, in 130 healthy children and upon intensive care unit (ICU) admission in 700 critically ill children of a randomized study on glycemic control. results: Levels of MASP-1, MASP-2, MASP-3, and MAp-44 were lower and the levels of M-ficolin were higher in ICU patients on admission than those in matched healthy controls. Only a low on-admission MASP-3 level was independently associated with risk of new ICU infections and prolonged ICU stay, after correcting for other risk factors. On-admission MASP-3 varied with age, illness severity, and genetic variation. conclusion: Low on-admission MASP-3 levels in critically ill children were independently associated with subsequent acquisition of infection and prolonged ICU stay. The biological explanation needs further investigation.
2016
Gene polymorphisms, giving rise to low serum levels of mannose binding lectin (MBL) or MBL-associated protease (MASP) 2, have been associated with an increased risk of infections. The objective of this study was to asses the outcome of intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS) regarding the existence of functionally relevant MBL2 and MASP2 gene polymorphisms. Methods: The study included 243 ICU patients with SIRS admitted to our hospital, as well as 104 healthy control subjects. MBL2 and MASP2 single nucleotide polymorphism´s were genotyped using a sequence-based typing technique. Results: No differences were observed regarding the frequencies of low-MBL genotypes (O/O and XA/O) and MASP2 polymorphisms between patients with SIRS and healthy controls. Interestingly, ICU patients with a non-infectious SIRS had a lower frequency for low-MBL genotypes and a higher frequency for high-MBL genotypes (A/A, A/XA) than either ICU patients with an infectious SIRS or healthy controls. The existence of low/high-MBL genotypes or MASP2 polymorphism had no impact in the mortality rates of the included patients. Conclusions: the presence of high-MBL producing genotypes in patients with a non-infectious insult is a risk factor for SIRS and ICU admission.
Human Molecular Genetics, 2007
Polymorphisms in the MBL2 gene, which affect the structure and influence on the serum concentration of mannose-binding lectin (MBL), are associated with inflammatory and infectious conditions. The importance of MBL2 polymorphisms on outcome in critical ill patients is unclear. Five hundred and thirty-two consecutive critically ill patients admitted to an intensive care unit (ICU) were included over a period of 18 months. Five hundred and thirty-three individuals served as controls. Vital status was obtained 15.5 months after the last patient was included. MBL2 polymorphisms were determined by a PCR-based assay. Homozygosity for MBL2 variant alleles (O/O) causing MBL structural defects was associated with the highest adjusted mortality rate followed by homozygosity for the normal MBL2 allele (A/A) encoding high MBL levels, whereas heterozygous A/O patients had the most favourable outcome (P 5 0.015). MBL2 alleles were not associated with death in ICU (n 5 166, P 5 0.7), but the association appeared soon after discharge from ICU (n 5 366): hazard ratio (HR) for O/O using A/A as reference was 1.33 (95% CI: 0.8 -2.2) and for A/O it was 0.62 (95% CI: 0.4 -0.8) respectively (P 5 0.0045) at completion. No difference in MBL2 frequency was observed between patients and controls at baseline, and between patients classified as having sepsis or not. However, patients with the MBL2 O/O genotype had an increased frequency of Gram-positive bacterial infection (P 5 0.01). Heterozygosity for MBL2 alleles confers a protective effect whereas homozygosity is associated with the worst outcome soon after discharge from ICU. This may be an example of heterosis.
Serum Mannose Binding Lectin Levels in Early Onset Neonatal Sepsis
American Journal of Health Research, 2015
Introduction: Early Onset Neonatal Sepsis (EONS) is still the most cause of neonatal morbidity and mortality. The diagnosis is difficult to establish because of nonspecific clinical features and laboratory findings. Mannose binding lectin (MBL) is one of the acute phase proteins that can show progressing infection process. Objective: To determine the serum MBL levels of neonates with EONS and not EONS. Methods: This study was conducted as a cross sectional study from September to November 2014. The population included 92 neonates baby whose mother has risk factors of sepsis and admitted to Dr. Wahidin Sudirohusodo Hospital and joined hospital. The subjects were divided into two groups, EONS and Not EONS group based on clinical features and laboratory findings. The MBL serum level was measured on each group. Results: Statistical analyses showed median value of serum MBL of EONS group (0.88 µg/mL) was significant lower compare with Not EONS group (0.93 µg/mL), with p= 0.00 (p<0.05). The cutoff point of ≤0.93 µg/mL is the best levels to distinguish between EONS and Not EONS (p=0.01, sensitivity 76%, specificity 56%, positive predictive value 60%, negative predictive value 67%, COR 3.182, 95%CI 1.306-7.752). Conclusion: MBL serum levels on EONS group were lower than Not EONS group.