Low Serum Mannose‐Binding Lectin Level Increases the Risk of Death due to Pneumococcal Infection

Eisen, Damon P.; Dean, Melinda M.; Boermeester, Marja A.; Fidler, Katy; Gordon, Anthony; Kronborg, Gitte; Kun, Jürgen F. J.; Lau, Yu Lung; Payeras, Antonis; Valdimarsson, H.; Brett, Stephen; Ip, W. K.; Milà, Joan; Peters, Mark; Saevarsdóttir, Saedís; Till, J. W. Olivier van; Hinds, C. J.; McBryde, Emma S.

doi:10.1086/590006

Cited by 164 publications

(169 citation statements)

References 42 publications

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“…Generally, with age, there is a decreasing trend in serum MBL concentrations. This finding is also in line with previous studies which show that the frequency of low serum MBL level (using the cut-off , 500 ng/ml) is ∼25% in the general population (12,20).…”

Section: Discussionsupporting

confidence: 93%

“…Mutant variants are unable to properly form the MBL molecule multimer; thus, the amount of functional MBL in blood and tissues decreases (10,11). MBL pathway deficiency is considered the most common congenital immunodeficiency of humans; it affects approximately one fourth of the general population (12,13).…”

Section: Yme Borreliosis (Lb) Is the Most Common Pathogenic Tick-mentioning

confidence: 99%

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Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Sajanti

Gröndahl-Yli-Hannuksela

Kauko

et al. 2015

The Journal of Immunology

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Risk factors for the widely endemic and much-debated tick-borne infection, Lyme borreliosis (LB), are unknown. The mannose-binding lectin (MBL) pathway of the complement cascade has an essential role in the eradication of Borrelia burgdorferi. A sufficient concentration of biologically active MBL in body fluids is an indicator of proper function of the MBL pathway. In this study, we investigated whether impaired MBL pathway function, represented by reduced serum MBL concentration, predisposes individuals to LB. First, we determined a serum MBL concentration cut-off level associated with diminished MBL pathway function in a group of 201 individuals. Then, we identified 350 borrelia Ab+ LB patient serum samples and 350 Ab− control samples from the archives of our laboratory and measured serum MBL concentrations in both sample groups. The concentration data were analyzed statistically using logistic regression, controlling for MBL cut-off, age, gender, and age and gender interaction. Serum MBL concentrations < 787 and < 445 ng/ml were associated with diminished and deficient MBL pathway function, respectively. Using these cut-offs, diminished (41.4 versus 27.4%, p = 0.0027) and deficient (26.3 versus 17.1%, p = 0.0361) MBL pathway functions were observed statistically more frequently in the LB patient samples than in the control samples. Also, the age-adjusted median serum MBL concentrations were significantly lower in the LB patient samples than in the non-LB controls. Our findings indicate that a deficiency in the MBL pathway of the complement cascade is a risk factor for developing disseminated Ab+ LB.

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Section: Discussionsupporting

confidence: 93%

Section: Yme Borreliosis (Lb) Is the Most Common Pathogenic Tick-mentioning

confidence: 99%

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Sajanti

Gröndahl-Yli-Hannuksela

Kauko

et al. 2015

The Journal of Immunology

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“…In a recent analysis of a large patient cohort it was shown that MBL serum levels can reliably indicate genetic MBL deficiency. 16 The ELISA we used strongly correlates with both the functional activity of the lectin pathway and the presence of low-producing MBL2 genotypes. 17 Furthermore, ELISA measurements of MBL allow an estimation of in vivo MBL status that may be caused by gene polymorphisms including, but not restricted to, the six well-known polymorphisms in the promoter and the first exon.…”

Section: Discussionmentioning

confidence: 99%

Mannose-binding lectin levels and infections in children after allogeneic hematopoietic SCT

Chaudhry

Jansen-Hoogendijk

Zijde

et al. 2009

Bone Marrow Transplant

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Mannose-binding lectin (MBL) is an activator of the lectin pathway of the C 0 system and hence an important component of the innate immune system. Although reports are conflicting, MBL deficiency has been reported to influence the infection susceptibility in hematology/ oncology patients or recipients of allogeneic hematopoietic SCT (HSCT). MBL levels and the occurrence of infections were retrospectively analyzed in 98 pediatric HSCT patients. MBL deficiency in recipients was not corrected by HSCT using a donor with normal MBL production. In addition, low serum MBL concentrations were not associated with increased susceptibility to any type of infections post-HSCT in this cohort of pediatric HSCT recipients.

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“…In recent years, the association between genetic variations in MBL2 , and to a lesser extent FCN2 , and susceptibility to disease have been the subject of various studies 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31. An association between MBL2 polymorphisms and clinical outcome has been described in children with recurrent infections22 and in adult patients with meningococcal sepsis 17…”

Section: Introductionmentioning

confidence: 99%

“…More recently, the role of MBL2 polymorphisms in invasive pneumococcal disease25, 27, 30, 31 and CAP23, 24 has been studied but with conflicting results. In addition, several studies show that MBL dysfunction is associated with a worse clinical outcome in patients with CAP, sepsis and bacteraemia 21, 24, 26. Only one study investigated the role of FCN2 polymorphisms in pneumococcal disease and showed no apparent relation 19…”

Section: Introductionmentioning

confidence: 99%

Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens

et al. 2017

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SummaryCommunity‐acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose‐binding lectin (MBL) and l‐ficolin (l‐FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.

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Low Serum Mannose‐Binding Lectin Level Increases the Risk of Death due to Pneumococcal Infection

Cited by 164 publications

References 42 publications

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Mannose-binding lectin levels and infections in children after allogeneic hematopoietic SCT

Mannose‐binding lectin and l‐ficolin polymorphisms in patients with community‐acquired pneumonia caused by intracellular pathogens

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