Low levels of mannose‐binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy

Bergmann, Olav J.; Christiansen, Michael; Laursen, Inga; Bang, Peter Fibiger; Hansen, Niels Ebbe; Ellegaard, Jørgen; Koch, Claus; Andersen, Vagn

doi:10.1034/j.1600-0609.2003.00012.x

Cited by 68 publications

(58 citation statements)

References 15 publications

(24 reference statements)

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“…The condition with more reduced dose of chemotherapy, conventional-dose chemotherapy without stem cell support, has been demonstrated to be at an increased risk of infection or prolonged fever in several reports, 13,14 but not by others. 17,27 Considering the strong association of MBL polymorphism and major bacterial infection in our patients, it is suggested that the protective role of MBL for infection might be more pronounced in the patients receiving HDT than those with conventional chemotherapy. However, it should be taken into consideration that the controversy about the relationship of MBL deficiency and infection after chemotherapy might be caused, at least in part, by the difference in the patients' profiles, such as underlying diseases, age, ethnicity, and other unknown genetic factors, between these several studies including ours.…”

Section: Increased Risk Of Infection In Mbl Polymorphismmentioning

confidence: 88%

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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Section: Increased Risk Of Infection In Mbl Polymorphismmentioning

confidence: 88%

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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“…Peterslund et al 20 found that patients with clinically significant infections after chemotherapy had significantly lower levels of MBL in serum, but later studies have been partly contradictory. Bergmann et al 21 found no indications of a protective effect of a high-serum MBL in patients with acute myeloid leukaemia (AML), and Kilpatrick et al 22 found only a weak association between low serum MBL and infections. In the latter study all infections, contracted in a study group of mixed haematological malignancies, were divided into four categories, and only the most severe category of infections was significantly more common in patients with low serum MBL.…”

Section: Introductionmentioning

confidence: 99%

“…The results indicated that highfunctioning MBL genes decrease the risk of major bacterial infections. 24 Only one of the earlier published studies was made on a uniform group of patients, namely patients with AML, 21 and new studies on the topic should probably relate to specific patient groups. In this study, we focus on the impact of MBL2 polymorphism on the risk of severe infections related to ASCT in patients with MM.…”

Section: Introductionmentioning

confidence: 99%

MBL2 polymorphism and risk of severe infections in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation

Mølle

Peterslund

Thiel

et al. 2006

Bone Marrow Transplant

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Severe infections related to treatment are common in patients with multiple myeloma (MM). Genetic polymorphisms of the immune system may influence the risk of infections. Mannan-binding lectin (MBL) is part of the innate immune system, and individuals homozygous for wild-type MBL encoding gene (MBL2) have a wellfunctioning MBL pathway of complement activation, in contrast to individuals carrying one or two variant alleles. We evaluated 113 courses of high-dose melphalan and autologous stem cell transplantation (ASCT) in patients with MM. Patients homozygous for wild-type MBL2 had a significantly reduced risk of septicaemia during the ASCT procedure compared with patients carrying variant MBL2: Odds Ratio (OR) 0.19 (95% CI: 0.04-0.77), (P ¼ 0.02) in multivariate analysis. The risk of Common Toxicity Criteria grade 3-4 infections in general was not affected by wild-type MBL2: OR 1.20 (95% CI: 0.52-2.78), (P ¼ 0.67). The findings indicate that MBL to some extent protects against the most severe infections during ASCT.

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“…The two promoter polymorphisms, Ϫ550 H/L and Ϫ221 X/Y, were combined to form three promoter haplotypes: HY, LY, and LX [12], which are related to high, intermediate, and low levels of MBL, respectively (Table 1) [18,21]. The HX haplotype probably does not occur in whites because of linkage disequilibrium [39,40].…”

Section: Construction Of Mbl2 Haplotypes and Phenotypesmentioning

confidence: 99%

“…This seems particularly relevant when a patient is under immunosuppressive therapy or is receiving a bone marrow transplant and/or chemotherapy for hematological malignancies [3, 6 -11]. However, research on the effects of MBL on hematological malignancies has yielded conflicting results [7,[12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia

Bol

Jong

Schaik³

et al. 2010

The Oncologist

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Objective. Mannose-binding lectin (MBL) is important in the innate immune response. MBL2 gene polymorphisms affect MBL expression, and genotypes yielding low MBL levels have been associated with an elevated risk for infections in hematological cancer patients undergoing chemotherapy. However, these reported associations are inconsistent, and data on patients with solid tumors are lacking. Here, we investigated the effects of MBL2 genotypes on irinotecan-induced febrile neutropenia in patients with solid tumors.Patients and Methods. Irinotecan-treated patients were genotyped for the MBL2 gene. Two promoter (؊550 H/L and ؊221 X/Y) and three exon polymorphisms (52 A/D, 54 A/B, and 57 A/C) were determined, together with known risk factors for irinotecan-induced toxicity. Neutropenia and febrile neutropenia were recorded during the first course.Results

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Low levels of mannose‐binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy

Cited by 68 publications

References 15 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

MBL2 polymorphism and risk of severe infections in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation

Effects of Mannose-Binding Lectin Polymorphisms on Irinotecan-Induced Febrile Neutropenia

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