Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome

Smithson, Àlex; Perelló, Rafael; Aibar, Jesús; Espinosa, Gerard; Tàssies, Dolors; Freire, Carolina; Castro, Pedro; Suárez, Belén; Lozano, Francisco; Nicolás, J.M.

doi:10.1128/cvi.00375-09

Cited by 9 publications

(11 citation statements)

References 59 publications

(83 reference statements)

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“…This is in agreement with our earlier observations, that postoperative SIRS is related to higher preoperative serum MBL levels and high MBL-producing genotypes [16]. Similar observations were reported by Smithson et al for adult ICU patients [15].…”

Section: Discussionsupporting

confidence: 94%

Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery

Pągowska‐Klimek

Świerzko

Michalski

et al. 2016

Clinical and Experimental Immunology

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SummaryThe systemic inflammatory response is a challenge in the management of paediatric patients undergoing cardiac surgery. Although multi-factorial, a contribution by the lectin pathway of complement activation has been postulated. We therefore investigated the changes in serum levels of mannose binding lectin (MBL) and activities of MBL-MBL-associated serine protease (MASP)-1 and MBL-MASP-2 complexes immediately before and during surgery, throughout the first postoperative day and at discharge from the hospital. These changes were analysed in relation to postoperative complications. Blood samples were obtained from 185 children with congenital heart disease undergoing surgical correction with the use of cardiopulmonary bypass: preoperatively (MBL-1), 15 min after initiation of cardiopulmonary bypass (CPB) (MBL-E), 30 min (MBL-2), 4 h (MBL-3), 12 h (MBL-4) and 24 h (MBL-5) post-CPB and at discharge from hospital (MBL-K). Alterations in serum MBL levels were calculated as a ratio of its serum level at subsequent time-points (MBL-2, -3, -4, -5) to the preoperative (MBL-1) value. Decreases in MBL and MBL-MASP complexes were observed in all samples, correlating with a decrease in C4 and increase in C4a, confirming activation of the lectin pathway. Changes in MBL levels between children with an uncomplicated postoperative course and those suffering from infection or low cardiac output syndrome did not differ significantly, but significant differences were observed between the SIRS and non-SIRS groups. Paediatric cardiac surgery with the use of cardiopulmonary bypass activates the complement system via the lectin pathway and the latter contributes to the development of the post-bypass systemic inflammatory response.

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Section: Discussionsupporting

confidence: 94%

Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery

Pągowska‐Klimek

Świerzko

Michalski

et al. 2016

Clinical and Experimental Immunology

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“…These data suggest that in the case of high-attack-rate serotypes, microbiological factors may proportionally have Our data about the implication of MBL in the development of IPD in young children are novel but in agreement with studies performed in mice about the role of MBL in susceptibility to pneumococcal infection [23]. Another study performed in our geographical area reported a similar percentage of 15.3% among adults [13]. A recent systematic review has reported a probable association between HIV disease progression and MBL deficiency, and this association was especially high in children <2 years of age [24].…”

Section: Discussionsupporting

confidence: 87%

“…It is considered a pre-antibody that has a relevant defensive role in the first period of life, when an immature adaptive immune system still exists. Previous reports indicate that genetically-determined MBL deficiency is relatively frequent in all human populations analyzed (ranging from <15% in Caucasian populations to 20% in sub-Saharan African populations) [13,14]. Homo-and heterozygous combinations of those SNPs give rise to different genotypes responsible for high (A/A, XA/A), intermediate (O/ A, XA/XA) or low (O/O, XA/O) serum MBL levels [12].…”

Section: Introductionmentioning

confidence: 99%

“…Homo-and heterozygous combinations of those SNPs give rise to different genotypes responsible for high (A/A, XA/A), intermediate (O/ A, XA/XA) or low (O/O, XA/O) serum MBL levels [12]. Previous reports indicate that genetically-determined MBL deficiency is relatively frequent in all human populations analyzed (ranging from <15% in Caucasian populations to 20% in sub-Saharan African populations) [13,14]. This deficiency has been linked to increased susceptibility to infectious diseases, including those caused by pneumococcus [15].…”

Section: Introductionmentioning

confidence: 99%

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High prevalence of genetically-determined mannose binding lectin deficiency in young children with invasive pneumococcal disease

Muñoz-Almagro¹,

Bautista

Arias

et al. 2014

Clinical Microbiology and Infection

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Susceptibility to invasive pneumococcal disease (IPD) correlates with age, younger children being the group with the highest burden of disease. The relevance of the innate immune response and particularly the role of mannose-binding lectin (MBL) in combating IPD is not well known. This is a 2-year prospective study (February 2011 to March 2013) including patients with IPD who attended two hospitals from Catalonia, Spain. Variables including attack rate of pneumococcal serotype (high or low invasive potential serotypes) and genotypes associated with low serum MBL levels were recorded. One hundred and forty-seven patients were included in the study. One hundred and two (69.4%) patients were children or adolescents <18 years and 45 (30.6%) were adults. Overall, low-MBL genotypes (O/O; XA/O) were detected in 23 (15.6%) patients. Children <2 years showed a higher frequency of low-MBL genotypes compared with other patients (31.0% vs. 11.9%; p = 0.031). Further sub-analysis revealed a higher proportion of low-MBL genotypes in children <2 years with IPD caused by opportunistic or low-attack-rate serotypes when compared with older patients (46.2% vs. 13.2%; p = 0.02). However, no statistically significant differences between the two groups were observed when including patients infected with invasive or high-attack-rate serotypes (18.8% vs. 10.0%; p = 0.59). Our data suggest that young children with a genetically determined low-MBL production are at a higher risk of developing IPD, particularly that caused by opportunistic or low-attack-rate pneumococcal serotypes.

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“…However, other studies in adults have not found MBL to be associated with risk for sepsis (39–42) or have reported a more nuanced picture that includes a mixture of both pro-inflammatory and anti-infection effects which may be beneficial or detrimental in varying disease states. (33, 34, 43) Specifically in pediatrics, six studies have demonstrated an association between lower MBL levels, or low-MBL producing haplotypes, and increased severity of infection-related disease (4, 5, 15, 16, 44–46) while five studies showed similar findings to ours with a lack of association (12, 46–50) and two studies concluded a possible protective role for low-producing MBL genotypes or levels. (12, 51)…”

Section: Discussionsupporting

confidence: 67%

Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections*

Madsen

Levy

Madden

et al. 2017

Pediatric Critical Care Medicine

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Objective Low mannose-binding lectin (MBL) levels and haplotypes associated with low MBL production have been associated with infection and severe sepsis. We tested the hypothesis that MBL levels would be associated with severe infection in a large cohort of critically ill children. Design Prospective cohort study Setting Medical and Surgical Pediatric Intensive Care Units (PICUs), Boston Children’s Hospital Patients Children < 21 years of age admitted to the intensive care units from November 2009 to November 2010. Interventions None Measurements and Main Results We measured MBL levels in 479/520 (92%) consecutively admitted children with severe or life-threatening illness. We genotyped 213 Caucasian children for MBL haplotype tagging variants and assigned haplotypes. In the univariate analyses of MBL levels with pre-admission characteristics, levels were higher in patients with pre-existing renal disease. Patients who received >100 ml/kg of fluids in the first 24 hours after admission had markedly lower MBL, as did patients post-spinal fusion surgery. MBL levels had no association with infection status on admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock. Although MBL haplotypes strongly influenced MBL levels in the predicted relationship, low MBL-producing haplotypes were not associated with increased risk of infection. Conclusions Mannose-binding lectin levels are largely genetically determined. This relationship was preserved in children during critical illness, despite the effect of large-volume fluid administration on MBL levels. Previous literature evaluating an association between MBL levels and severe infection is inconsistent; we found no relationship in our PICU cohort. We found that MBL levels were lower after aggressive fluid resuscitation, and suggest that studies of MBL in critically ill patients should assess MBL haplotypes to reflect pre-illness levels.

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Genotypes Coding for Low Serum Levels of Mannose-Binding Lectin Are Underrepresented among Individuals Suffering from Noninfectious Systemic Inflammatory Response Syndrome

Cited by 9 publications

References 59 publications

Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery

Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery

High prevalence of genetically-determined mannose binding lectin deficiency in young children with invasive pneumococcal disease

Mannose-Binding Lectin Levels in Critically Ill Children With Severe Infections*

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