Analysis of the Relationship Between Mannose‐Binding Lectin (MBL) Genotype, MBL Levels and Function in an Australian Blood Donor Population

Minchinton, R. M.; Dean, Melinda M.; Clark, Trevor; Heatley, Sue L.; Mullighan, Charles G.

doi:10.1046/j.1365-3083.2002.01167.x

Cited by 177 publications

(225 citation statements)

References 36 publications

(61 reference statements)

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“…Generally, with age, there is a decreasing trend in serum MBL concentrations. This finding is also in line with previous studies which show that the frequency of low serum MBL level (using the cut-off , 500 ng/ml) is ∼25% in the general population (12,20).…”

Section: Discussionsupporting

confidence: 93%

“…As explained in Materials and Methods, the age distribution was intentionally different between the groups; therefore, the statistical analyses performed were adjusted for age. According to our data, low serum MBL levels occurred in ∼25-30% of the non-LB control samples throughout the age groups, which is in agreement with previous studies in the general population (12,20). According to a survey conducted in a general Finnish population by Aittoniemi et al (22), the highest serum MBL concentrations were detected in early childhood, after which there was a decline in serum MBL levels with age.…”

Section: Discussionsupporting

confidence: 92%

“…For this reason, we also selected non-LB control samples from sera that were sent to our laboratory for testing of borrelia serology instead of using data from blood donor samples. Among the non-LB control samples, the frequency of low MBL concentration in each age group corresponded with the occurrence of low MBL concentration in the general population (12,20). This indicates that low serum MBL levels among the LB patient samples are indeed associated with LB infection and are not due to any bias in sample selection.…”

Section: Discussionmentioning

confidence: 71%

“…However, our analysis showed an obvious association between MBL pathway function and serum MBL concentration. In addition, based on previous studies, it is recommended to use either a low serum MBL level or a direct functional assessment of the MBL pathway as an indicator of diminished MBL pathway function, instead of genotyping, when examining disease associations (12,20). Third, because the borrelia-expressed ligand that interacts with MBL has not been identified and because LB in Europe is caused mainly by B. garinii and B. afzelii, a similar study should be performed in the United States to investigate whether deficient MBL pathway of the complement cascade also is a risk factor in patients in an area in which B. burgdorferi sensu stricto is the only encountered genospecies.…”

Section: Discussionmentioning

confidence: 99%

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Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Sajanti

Gröndahl-Yli-Hannuksela

Kauko

et al. 2015

The Journal of Immunology

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Risk factors for the widely endemic and much-debated tick-borne infection, Lyme borreliosis (LB), are unknown. The mannose-binding lectin (MBL) pathway of the complement cascade has an essential role in the eradication of Borrelia burgdorferi. A sufficient concentration of biologically active MBL in body fluids is an indicator of proper function of the MBL pathway. In this study, we investigated whether impaired MBL pathway function, represented by reduced serum MBL concentration, predisposes individuals to LB. First, we determined a serum MBL concentration cut-off level associated with diminished MBL pathway function in a group of 201 individuals. Then, we identified 350 borrelia Ab+ LB patient serum samples and 350 Ab− control samples from the archives of our laboratory and measured serum MBL concentrations in both sample groups. The concentration data were analyzed statistically using logistic regression, controlling for MBL cut-off, age, gender, and age and gender interaction. Serum MBL concentrations < 787 and < 445 ng/ml were associated with diminished and deficient MBL pathway function, respectively. Using these cut-offs, diminished (41.4 versus 27.4%, p = 0.0027) and deficient (26.3 versus 17.1%, p = 0.0361) MBL pathway functions were observed statistically more frequently in the LB patient samples than in the control samples. Also, the age-adjusted median serum MBL concentrations were significantly lower in the LB patient samples than in the non-LB controls. Our findings indicate that a deficiency in the MBL pathway of the complement cascade is a risk factor for developing disseminated Ab+ LB.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Sajanti

Gröndahl-Yli-Hannuksela

Kauko

et al. 2015

The Journal of Immunology

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“…C4 deposition was measured using ELISA as previously described 13 which arbitrarily quantifies C4 deposited onto a solid phase mannan surface. After MBL binding to mannan, subsequent C4 deposition was measured using a biotinylated anti-C4 antibody (Sigma-Aldrich, Castle Hill, NSW, Australia).…”

Section: Complement Activation Assaymentioning

confidence: 99%

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Hodge

Dean

Hodge

et al. 2011

The Journal of Heart and Lung Transplantation

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Short running title: Decreased efferocytosis and MBL in BOSwith BOS) and 14 healthy controls. Abstract & Manuscript 2Results: In plasma, MBL levels were highly variable (0-17.538 g/mL), but increased in infected subjects vs control (p=0.09) or stable groups (p=0.003). There was a similar increase in UC4 in infected patients and a significant correlation between MBL and UC4. There was no correlation between MBL and time post-transplant. In BAL, MBL levels were less variable (0-73.3 ng/mL) and significantly reduced in patients with BOS vs controls and stable groups. 3Lung transplantation is now recognized as an effective treatment option for a variety of end-stage lung diseases and is associated with improvements in life expectancy and quality of life. However the five-year survival is currently only around 60%, the worst of any solid organ transplant, with death beyond the acute phase being largely due to progressive and treatment refractory airway remodeling (obliterative bronchiolitis, OB) manifest clinically as bronchiolitis obliterans syndrome (BOS). BOS is thought to follow persistent alloreactive, infective, and non-specific epithelial injury with dysregulated epithelial repair 1 . Although the predominant histopathologic finding in patients with OB is of fibro-proliferative small airway obliteration, large airways are also affected with the eventual development of bronchiectasis, leading directly to patient morbidity and mortality.The well-ordered process of apoptosis is important for regulation and maintenance of normal tissue homeostasis. During resolution of airway inflammation, apoptotic epithelial cells are removed by phagocytosis by alveolar macrophages (a process termed 'efferocytosis'). The pathological concept of failed efferocytosis has been described in regard to a number of lung diseases including pulmonary fibrosis 2 , cystic fibrosis 3 chronic granulomatous disease 4 smokers and patients chronic obstructive pulmonary disease (COPD) 5-8 .It is considered that the failed efferocytosis results in a net increase in apoptotic material that may lead to secondary necrosis of this material resulting in increased tissue damage and chronic inflammation. This was clearly shown in our studies of COPD where we found evidence of secondary necrosis (increased lactate dehydrogenase in BAL) and that the increased numbers of apoptotic bronchial epithelial cells negatively correlated with efferocytosis 6,9 . In lung transplant recipients we have also described an accumulation of apoptotic material associated with an increase in the cytotoxic mediator granzyme b in the airways 10,11 .Mannose binding lectin (MBL) is a key mediator of both innate immunity and efferocytosis and is thus likely to be important in protecting against lung tissue damage. In other inflammatory chronic lung diseases including COPD, we have shown reduced levels of MBL that correlated with a defect in the 4 ability of alveolar macrophages to phagocytose apoptotic bronchial epithelial cells (efferocytosis) 8 . We further showed that treatm...

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Complement: Measurement

North¹

2010

Encyclopedia of Life Sciences

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The complement system comprises a group of serum proteins and cell membrane receptors that function primarily to fight infection. Clinically, measurement of complement pathway activity and individual component levels is of value in (i) cases of suspected immunodeficiency with deficiencies of soluble components, including lectins, and of receptors leading to particular patterns of infection and (ii) conditions that involve complement activation such as systemic lupus erythematosis and renal translantion. This article describes functional and immunochemical methods that can be established in‐house or are available commercially. Until recently, measurement of complement in clinical situations has been aimed at identifying deficiency, of either level or function or activation. Mutations resulting in increased function have been identified for one component and this has opened a new area of research with clinical implications. Key Concepts: Correct sample collection and storage is essential for measurement of complement. Immunochemical measurement of circulating complement components can be performed by commercial assays, usually ELISA. Functional complement assays are required to detect deficiencies that do not affect immunochemical levels. Functional complement assays require buffers that are of the correct ionic strength and provide the requisite ions as well as being of the correct pH. Biosensor assays allow affinity and kinetic studies of complement component interaction.

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Analysis of the Relationship Between Mannose‐Binding Lectin (MBL) Genotype, MBL Levels and Function in an Australian Blood Donor Population

Cited by 177 publications

References 36 publications

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Decreased efferocytosis and mannose binding lectin in the airway in bronchiolitis obliterans syndrome

Complement: Measurement

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