MBL genotype and risk of invasive pneumococcal disease: a case-control study

Roy, Suchismita; Knox, Kyle; Segal, Shelley; Griffiths, David; Moore, Catrin E.; Welsh, Kenneth I.; Smarason, Alex; Day, Nicholas P. J.; McPheat, William L.; Crook, Derrick W.; Hill, Adrian V. S.

doi:10.1016/s0140-6736(02)08516-1

Cited by 286 publications

(215 citation statements)

References 33 publications

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“…In mammals, MBL functions as part of the innate immune system through the lectin complement pathway, and bacteria, yeast, parasites, mycobacteria and viruses are recognised by MBL (Crouch and Wright, 2001;Holmskov et al, 2003;Turner, 2003). MBL levels contribute to the severity of illness in several bacterial infections (Hibberd et al, 1999;Roy et al, 2002;Kars et al, 2005) and low MBL levels are associated with increased risk, severity and frequency of some infections (Botto et al, 2009). In fish species MBL have been reported in trout, salmon, carp, rohu fish, channel catfish, blue 16 catfish and sea lamprey (Jensen et al, 1997;Ewart et al, 1999;Vitved et al, 2000;Mitra and Das, 2002;Ourth et al, 2007Ourth et al, , 2008 and functional binding studies to fish pathogens have suggested a similar lectin complement pathway for these species (Ewart et al, 1999;Ourth et al, 2007Ourth et al, , 2008.…”

Section: Discussionmentioning

confidence: 99%

Molecular profiling of the gilthead sea bream (Sparus aurata L.) response to chronic exposure to the myxosporean parasite Enteromyxum leei

Davey¹,

Calduch-Giner²,

Houeix³

et al. 2011

Molecular Immunology

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Section: Discussionmentioning

confidence: 99%

Molecular profiling of the gilthead sea bream (Sparus aurata L.) response to chronic exposure to the myxosporean parasite Enteromyxum leei

Davey¹,

Calduch-Giner²,

Houeix³

et al. 2011

Molecular Immunology

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“…9,10 Low-producing MBL2 polymorphisms have been associated with frequency of respiratory tract infections in children, 11 earlier onset of infection, particularly pneumonia, in adults with systemic lupus erythematosus, 12 and higher risk of invasive pneumococcal disease. 13 Children carrying MBL2 variant alleles had prolonged febrile neutropenia during chemotherapy. 14 In cystic fibrosis (CF), MBL2 variant alleles were associated with impaired lung function and greater mortality.…”

Section: Introductionmentioning

confidence: 99%

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

et al. 2003

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Infection frequently causes exacerbations of chronic obstructive pulmonary disease (COPD). Mannose-binding lectin (MBL) is a pattern-recognition receptor that assists in clearing microorganisms. Polymorphisms in the MBL2 gene reduce serum MBL levels and are associated with risk of infection. We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility. Polymorphism frequency was determined by PCR-RFLP in 200 COPD patients and 104 smokers with normal lung function. Serum MBL was measured as mannan-binding activity in a subgroup of 82 stable COPD patients. Frequency of COPD admissions for infective exacerbation was ascertained for a 2-year period. The MBL2 codon 54 B allele reduced serum MBL in COPD patients. In keeping, patients carrying the low MBL-producing B allele had increased risk of admission for infective exacerbation (OR 4.9, P corrected ¼ 0.011). No association of MBL2 genotype with susceptibility to COPD was detected. In COPD, serum MBL is regulated by polymorphism at codon 54 in its encoding gene. Low MBL-producing genotypes were associated with more frequent admissions to hospital with respiratory infection, suggesting that the MBL2 gene is disease-modifying in COPD. MBL2 genotype should be explored prospectively as a prognostic marker for infection risk in COPD.

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“…The interest in the potential role of MBL in the pathophysiology of CAP was aroused by the finding that patients with an MBL2 ‐deficient genotype (0/0) were at risk for invasive pneumococcal disease 30. Although several later studies failed to confirm this result,25, 27, 31 a meta‐analysis of all these studies did show a significant association between MBL2 ‐deficient genotypes and susceptibility to invasive pneumococcal disease 25.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…FCN2 SNPs have been associated with a number of clinical conditions, including rheumatic fever,29 Behçet's disease,20 peritonitis in patients undergoing peritoneal dialysis28 and recurrent respiratory infections in children 16, 18. 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.…”

Section: Introductionmentioning

confidence: 99%

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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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MBL genotype and risk of invasive pneumococcal disease: a case-control study

Cited by 286 publications

References 33 publications

Molecular profiling of the gilthead sea bream (Sparus aurata L.) response to chronic exposure to the myxosporean parasite Enteromyxum leei

Molecular profiling of the gilthead sea bream (Sparus aurata L.) response to chronic exposure to the myxosporean parasite Enteromyxum leei

Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

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

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