Mannose-binding lectin: the pluripotent molecule of the innate immune system

Turner, Malcolm

doi:10.1016/s0167-5699(96)80908-x

Cited by 586 publications

(429 citation statements)

References 64 publications

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“…1,2 The carbohydrate recognition domain of MBL binds to high mannose and N-acetyl-glucosamine oligosaccharides on various microorganisms, while the collagen-like domain is considered to bind to its receptors on phagocytes. 1,3 MBL activates complement independently of antibodies, which is a third pathway (lectin pathway) distinct from the classical and alternative complement activation cascade. It is therefore considered that MBL is an apical and important component of innate immunity of host defense.…”

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confidence: 99%

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

et al. 2005

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A growing body of evidence indicates that genetic factors are involved in an increased risk of infection. We investigated whether mannose-binding lectin (MBL) gene polymorphisms that cause low levels of MBL are associated with the occurrence of major infections in patients, mainly bearing hematological malignancies, after high-dose chemotherapy (HDT) rescued by autologous peripheral blood stem cell transplantation (auto-PBSCT). A retrospective evaluation of 113 patients treated with HDT and auto-PBSCT revealed that the low-producing genotypes, B/B and B/LXA, were associated with major bacterial infection (P ¼ 0.0016, OR 7.9). We next performed a nation-wide large-scale study to assess the allele frequency of the MBL coding mutation in a total of 2623 healthy individuals in Japan. The frequency of allele B was estimated to be B0.2, almost the same in seven different areas of Japan. This common occurrence suggests that MBL deficiency may play an important role in the clinical settings of immunosuppression. Genes and Immunity (2005) The carbohydrate recognition domain of MBL binds to high mannose and N-acetyl-glucosamine oligosaccharides on various microorganisms, while the collagen-like domain is considered to bind to its receptors on phagocytes. 1,3 MBL activates complement independently of antibodies, which is a third pathway (lectin pathway) distinct from the classical and alternative complement activation cascade. It is therefore considered that MBL is an apical and important component of innate immunity of host defense. MBL has been shown to bind to a wide range of microorganisms including fungi, bacteria, protozoa, and viruses. 4 The serum level of MBL is dependent on various factors such as polymorphisms (in the coding region) and ethnicity and age (in the promoter region). [5][6][7] Of these factors, the structural polymorphisms at codons 52, 54, and 57 in the coding region are the most important determinants. All the three polymorphisms are caused by a single amino-acid substitution and result in the profound decrease of serum MBL in the individuals carrying the polymorphisms homozygously. Two polymorphisms in the promoter region at positions À550 and À221 also have additional, but less pronounced effects on the serum level of MBL. 5 Individuals carrying either of these three codon variants homozygously are common in different ethnic groups from 5 to 10%. 4 MBL deficiency is associated with infection in infants with immature immunity, 8,9 and patients with autoimmune disorders 10 and cystic fibrosis. 11,12 An association of MBL deficiency and infection is also reported in patients treated with conventional chemotherapy 13,14 or high-dose myeloablative chemotherapy followed by allogeneic stem cell transplantation, 15 which is not confirmed by others. 16,17 In the present study, we report an increased risk of major bacterial infection in patients carrying the MBL polymorphism when treated with high-dose chemotherapy (HDT) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). In ad...

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confidence: 99%

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

et al. 2005

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“…In addition, we found an association of BPD with the X-variant allele in the promotor region (rs7096206; À221), which has been shown to be associated with reduced MBL serum levels (for review see Turner 1 and Turner and Hamvas 4 ).…”

Section: Discussionmentioning

confidence: 94%

“…In individuals homozygous for this variant, there is evidence for small amounts of protein with a molecular weight close to 100 kDa, but there is relatively little stable assembly of higher order oligomers and lack of complement activation. Serum levels were shown to be reduced to one fourth in the presence of this variant (for review see Turner 1 and Turner and Hamvas 4 ). Association between MBL and pulmonary morbidity in preterms A Hilgendorff et al…”

Section: Discussionmentioning

confidence: 99%

“…1 With multiple carbohydrate-recognition domains, MBL is able to bind to sugar groups displayed on the surfaces of various pathogens and thereby provide firstline defense. MBL also activates the complement system through a distinctive third pathway, independent of both antibody and the C1 complex.…”

Section: Introductionmentioning

confidence: 99%

“…Three single-nucleotide polymorphisms (SNPs) in codons 52, 54 and 57 (D, B and C variants, respectively, with variant A indicating the wild-type and the three variant alleles collectively termed O) of exon 1 are believed to impair oligomerization and lead to a functional deficiency of MBL. 1,4 The B and C mutations result in the replacement of axial glycines in the triple helix by dicarboxylic acids. 5 In contrast, the D mutation results in the replacement of an amino acid (arginine with cysteine) hindering higher oligomer formation.…”

Section: Introductionmentioning

confidence: 99%

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Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants

et al. 2007

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Deficiency in the collectin mannose-binding lectin (MBL) increases the risk for pulmonary and systemic infections and its complications in children and adults. The aim of this prospective cohort study was to determine the genetic association of sequence variations within the MBL gene with systemic infections and pulmonary short-and long-term complications in preterm infants below 32 weeks gestational age (GA). Three single-nucleotide polymorphisms (SNPs) in the coding region and one SNP in the promotor region of MBL2 were genotyped by direct sequencing and with sequence-specific probes in 284 newborn infants o32 weeks GA. Clinical variables were comprehensively monitored. An association was found between two SNPs and the development of bronchopulmonary dysplasia (BPD), defined as persistent oxygen requirement at 36 weeks postmenstrual age, adjusting for covariates GA, grade of respiratory distress syndrome and days on mechanical ventilation (rs1800450 (exon 1 at codon 54, B variant): odds ratio dominant model (OR) ¼ 3.59, 95% confidence interval (CI) ¼ 1.62-7.98; rs7096206 (À221, X variant): OR ¼ 2.40, 95% CI ¼ 1. 16-4.96). Haplotype analyses confirmed the association to BPD, and a single haplotype (frequency 56%) including all SNPs in their wild-type form showed a negative association with the development of BPD. We detected no association between the MBL gene variations and the development of early-onset infections or further pulmonary complications. Frequent variants of the MBL gene, leading to low MBL concentrations, are associated with the diagnosis of BPD in preterm infants. This provides a basis for potential therapeutic options and further genetic and proteomic analysis of the function of MBL in the resistance against pulmonary long-term complications in preterm infants.

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Acute Respiratory Tract Infections and Mannose-Binding Lectin Insufficiency During Early Childhood

Koch

Melbye²,

Sørensen³

et al. 2001

JAMA

391

312

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Mannose-binding lectin: the pluripotent molecule of the innate immune system

Cited by 586 publications

References 64 publications

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

Association of polymorphisms in the mannose-binding lectin gene and pulmonary morbidity in preterm infants

Acute Respiratory Tract Infections and Mannose-Binding Lectin Insufficiency During Early Childhood

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