Mannose-binding lectin deficiency—revisited

Garred, Peter; Larsen, Frank Wugt; Madsen, Hans O.; Koch, Claus

doi:10.1016/s0161-5890(03)00104-4

Cited by 362 publications

(390 citation statements)

References 32 publications

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“…32 In addition, functional assays based on MBL binding to, for example, mannan preferentially reflect higher oligomers because of lower avidity towards mannan for higher compared to lower-order oligomerized MBL. Biochemical analyses have indicated that the most important quantitative effect of these structural variant alleles in vivo in man is a reduction of the protein concentration; however, trace amounts of low molecular weight material from carriers of these variant alleles have been observed.…”

Section: Consequences Of Mbl2 Gene Variations On Mbl Serum Levelsmentioning

confidence: 99%

Mannose-binding lectin and its genetic variants

et al. 2006

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Mannose-binding lectin (MBL) is a collagen-like serum protein that mediates activation of the complement system and is of importance for host defence. Common variant alleles situated both in the promoter and structural region of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variation in MBL serum concentration influences the susceptibility to and the course of different types of infections, autoimmune, metabolic and cardiovascular diseases, but this is still a subject of debate. The fact that these genetic variations are very frequent indicates a dual role for MBL in host defence. In this survey, we summarize the current molecular understanding of human MBL genetics.

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Section: Consequences Of Mbl2 Gene Variations On Mbl Serum Levelsmentioning

confidence: 99%

Mannose-binding lectin and its genetic variants

et al. 2006

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“…[29][30][31] Plasma levels and functional activity of the collectins are known to be determined by polymorphisms in exon 1 and in the promotor region of the MBL2 gene, and thus a genetic susceptibility to the development of severe infections has been suggested as genetic variants associated with low MBL concentrations revealed a clinical phenotype. 3,[7][8][9][10] Preterm infants, known to exhibit a markedly increased risk for the development of severe infections, may critically depend on their innate immune response, as the presence of early-onset and nosocomial infections mainly determines acute and long-term morbidity and mortality in this population, especially regarding the development of neurological and pulmonary impairment. [17][18][19] Especially, the development of chronic lung disease in preterm infants is known to be triggered by infectious complications and ongoing inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

“…There is a strong association between MBL SNPs and haplotypes and the serum level of the MBL protein. 7 Numerous disease association studies suggested an important role for MBL in relation to the acquisition or the clinical course of infectious diseases in children and adults. 3,[7][8][9][10] Especially in immunocompromised individuals, MBL deficiency appears to exert effects on susceptibility and severity of infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

“…7 Numerous disease association studies suggested an important role for MBL in relation to the acquisition or the clinical course of infectious diseases in children and adults. 3,[7][8][9][10] Especially in immunocompromised individuals, MBL deficiency appears to exert effects on susceptibility and severity of infectious diseases. [11][12][13][14][15][16] Because their adaptive immunity has not yet been developed, MBL is particularly important in neonates in whom immune defense depends on maternal antibodies and innate defense mechanisms.…”

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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“…Interestingly, case 2, who also had low levels of circulating MBL, presented the haplotype 4P-57Glu. To our knowledge, only a few of the theoretically possible MBL haplotypes have been described [19] and the 4P-57Glu haplotype has never been detected. It is unclear whether the low MBL levels may really be due to this particular haplotype.…”

Section: Discussionmentioning

confidence: 96%

Systemic lupus erythematosus as a first presentation of common variable immunodeficiency associated with infrequent mannose-binding lectin gene polymorphisms

et al. 2009

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The association of common variable immunodeficiency (CVID) and Systemic Lupus Erythematosus (SLE) is infrequent. Mannose-binding lectin (MBL) has been shown to play a role in CVID and SLE. The purpose of this study is to describe two cases of CVID who presented as SLE and also evaluate the presence of MBL polymorphisms and MBL serum levels in those patients.In both patients, SLE was the first manifestation of CVID. In these patients the SLE immunological markers and disease activity disappeared after the development of CVID. They carried the very infrequent MBL haplotype 4Q-57Glu. One of them had a homozygous genotype, whereas the other patient was heterozygous and also presented the haplotype 4P-57Glu that had never been previously detected. Interestingly, this last patient was presenting frequent respiratory tract infections, developed brochiectasis and had low levels of circulating MBL.These results may support the role of MBL in the development of autoimmunity in CVID. Further genetic studies are needed to clarify the role of the MBL polymorphisms in the development of autoimmunity in CVID.

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Mannose-binding lectin deficiency—revisited

Cited by 362 publications

References 32 publications

Mannose-binding lectin and its genetic variants

Mannose-binding lectin and its genetic variants

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

Systemic lupus erythematosus as a first presentation of common variable immunodeficiency associated with infrequent mannose-binding lectin gene polymorphisms

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