Mannan-binding lectin deficiency — Good news, bad news, doesn't matter?

Heitzeneder, Sabine; Seidel, Markus G.; Förster-Waldl, Elisabeth; Heitger, Andreas

doi:10.1016/j.clim.2011.11.002

Cited by 143 publications

(165 citation statements)

References 146 publications

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“…rheumatoid arthritis (Graudal et al, 1998, Martiny et al, 2012 and SLE (Davies et al, 1995;Sullivan et al, 1996;Glesse et al, 2011)) and infectious disorders (e.g. lung infection, septicaemia, and meningitis (Garred et al, 1995;Summerfield et al, 1997;reviewed in Turner, 2003;Sim et al, 2006;Heitzeneder et al, 2012)). However, the high frequency (~5% worldwide) of MBL homozygous deficiency in normal individuals indicates that the MBL-mediated complement activation pathway may be of considerable importance for opsonisation in individuals with immature or deficient immune systems.…”

Section: Components Of the Lectin Pathwaymentioning

confidence: 99%

“…Clinically significant deficiencies of some components do not always coincide with protein deficiencies, but rather with their inability to execute corresponding functions. For instance, MBL B, C, and D variants may exist as low order oligomers and fail to activate the complement cascade (Heitzeneder et al, 2012). The MASP-2 120G variant cannot associate with MBL and activate the complement (Stengaard-Pedersen et al, 2003)).…”

Section: Introductionmentioning

confidence: 99%

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Complement genetics, deficiencies, and disease associations

Mayilyan

2012

Protein Cell

147

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The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

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Section: Components Of the Lectin Pathwaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Complement genetics, deficiencies, and disease associations

Mayilyan

2012

Protein Cell

147

View full text Add to dashboard Cite

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“…Conversely, both low MBL levels, as well as specific MBL genotypes, in which the altered secondary structure of the collagenous region of MBL weakens MBL binding to MASPs, result in an impaired activation of the lectin pathway (reviewed in ref. 1) and might reduce the development and progression of GvHD.…”

Section: Resultsmentioning

confidence: 99%

Mannan-binding lectin deficiency attenuates acute GvHD in pediatric hematopoietic stem cell transplantation

Heitzeneder

Zeitlhofer²,

Pötschger

et al. 2015

Bone Marrow Transplant

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“…A generally accepted cut-off serum MBL concentration required for a normally activated MBL pathway has not been determined, and the cut-off levels for low MBL concentrations vary among studies (19). Based on the functional assessment of the MBL pathway, we determined that serum MBL levels , 787 and , 445 ng/ml are associated with diminished and deficient functions of the MBL pathway, respectively.…”

Section: Discussionmentioning

confidence: 99%

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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Mannan-binding lectin deficiency — Good news, bad news, doesn't matter?

Cited by 143 publications

References 146 publications

Complement genetics, deficiencies, and disease associations

Complement genetics, deficiencies, and disease associations

Mannan-binding lectin deficiency attenuates acute GvHD in pediatric hematopoietic stem cell transplantation

Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

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