Reconstitution of Opsonizing Activity by Infusion of Mannan‐Binding Lectin (MBL) to MBL‐Deficient Humans

Valdimarsson, H.; Stefansson, M; Vikingsdottir, T.; Arason, G J; Koch, Christian; Thiel, Steffen; Jensenius, Jens C.

doi:10.1046/j.1365-3083.1998.00396.x

Cited by 120 publications

(86 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This phenomenon is consistent with findings of previous reports [31][32][33]. So far, only a single peak at a high-molecular-mass position was reported for purified serum MBL in humans [34][35][36][37] and other species [37][38][39]. It is simply thought that low-molecular-mass MBL (corresponding to peak 2) was overlooked because it did not bind to the carbohydrate resin, and only the fractions which did bind to the resin (corresponding to peak 1) were able to proceed to the next step in purification or identification.…”

Section: Discussionsupporting

confidence: 93%

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

et al. 2003

View full text Add to dashboard Cite

Mannose-binding lectin (MBL) activates complement through MBL-associated serine proteases (MASP). A deficiency in MBL due to mutations at exon 1 of the human MBL gene is reported to cause vulnerability to infection. We examined sera of known MBL genotype by gel filtration and assessed their elution patterns using an ELISA for MBL and identified two MBL forms, a high-molecular-mass form and a lower-molecular-mass form. By the identification of either or both forms in individual sera, three types of patterns emerged: type 1 consisted of a high-molecular form; type 2, of a low-molecular form; and type 3, of both forms. Types 1, 2 and 3 corresponded, respectively, to a wild type (A/A), a homozygous mutation at codon 54 (B/B) and their heterozygote (A/B). One exception was a heterozygous LXPA/LYPB phenotype that exhibited the type-2 pattern. Binding to mannan and MASP-1/3 occurred exclusively with the high-molecular form. An apparent MBL deficiency does not in fact represent a deficiency in MBL molecules but rather the presence of circulating oligomeric mutant MBL with impaired function.

show abstract

Section: Discussionsupporting

confidence: 93%

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

et al. 2003

View full text Add to dashboard Cite

show abstract

“…MBL replacement has been suggested as novel therapy in immunocompromised patients, 14 especially those at high risk of infection because of MBL insufficiency. Short-term administration of purified MBL from pooled donor plasma had a satisfactory safety profile and some observable efficacy in two MBL-deficient individuals 25 and a patient with severe CF. 26 If prospective studies confirm MBL2 polymorphisms as risk stratification factors in COPD, MBL replacement may provide targeted therapy for genetically susceptible, MBLdeficient COPD patients with frequent respiratory infections.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

View full text Add to dashboard Cite

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.

show abstract

“…In fact, plasma-derived MBL has already been administered to a number of healthy volunteers 30 or selected patients 31 without adverse effects. It would be important to more clearly define subsets of MBL-deficient patients who are at increased risk of infection after chemotherapy and are thus treated effectively with MBL replacement therapy.…”

Section: Increased Risk Of Infection In Mbl Polymorphismmentioning

confidence: 99%

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

et al. 2005

View full text Add to dashboard Cite

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...

show abstract

Reconstitution of Opsonizing Activity by Infusion of Mannan‐Binding Lectin (MBL) to MBL‐Deficient Humans

Cited by 120 publications

References 41 publications

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

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

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

Contact Info

Product

Resources

About