Clinical manifestation of mannose-binding lectin deficiency in adults independent of concomitant immunodeficiency

Hoeflich, Conny; Unterwalder, Nadine; Schuett, Sabine; Schmolke, Kathrin; Boenisch, Olaf; Hammer, Markus; Scheufele, Ramona; Michael, Dagmar; Volk, Hans‐Dieter; Scheibenbogen, Carmen; Baehr, Volker von; Meisel, Christian

doi:10.1016/j.humimm.2009.07.003

Cited by 19 publications

(19 citation statements)

References 23 publications

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“…Our results on high occurrence of respiratory tract infections in adult MBL deficient individuals support previous findings [44]. However, our MBLD cohort was more frequently diagnosed with sinusitis than previously reported [44].…”

Section: Discussionsupporting

confidence: 91%

“…In addition, we found that the infections were recurrent and severe in the MBLD cohort. Furthermore, we showed that MBLD individuals with the O/O genotype were significantly more likely to suffer from oesophagitis and gastritis as well having undergone gastroscopy than MBLD individuals with the A/O and A/A genotypes.Our results on high occurrence of respiratory tract infections in adult MBL deficient individuals support previous findings [44]. However, our MBLD cohort was more frequently diagnosed with sinusitis than previously reported [44].…”

supporting

confidence: 91%

“…However, our MBLD cohort was more frequently diagnosed with sinusitis than previously reported [44]. The high insidence of tonsillectomy and adenoidectomy among MBL deficient individuals has also been previously observed among MBLD individuals [45].…”

Section: Discussionsupporting

confidence: 67%

“…It has been shown that pneumonia caused by Streptococcus pneumoniae is linked to the O allele and low MBL levels increases the death due to pneumococcal infection [21,46]. Since our questionnarie was retrospective it is not possible to identify the underlying cause of pneumonia of our study cohort.Previous studies have also reported significantly increased frequency of severe MBL deficiency (MBL levels ≤ 50 ng/ml) in adult patients with a history of recurrent/and or severe infections, including pneumonia and bronchitis [44]. In that study, it was ascertained that the patients neither had concomitant immunodeficiencies nor had received immunosuppressive therapy [44].…”

mentioning

confidence: 97%

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Mannan-Binding Lectin (MBL) Deficient Individuals with the O/O Genotype are Highly Susceptible to Gastrointestinal Diseases

Thorsteinsdottir¹

2014

J Clin Cell Immunol

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Background: Mannan-binding lectin (MBL) and ficolin-3 are initiators of the lectin pathway that is important for clearance of pathogens and apoptotic cells through complement activation. MBL deficiency (MBLD) has been associated with infectious complications but its clinical relevance in adults is unclear. Definition of MBLD is commonly linked to its low serum levels, but is mainly due to functional polymorphisms in the MBL2 gene leading to dysfunctional MBL forms. Homozygotes for dysfunctional alleles (O/O) have the lowest serum levels (<50 ng/ml) with a defect in opsonisation and complement activation. Ficolin-3 deficiency due to homozygosity of a frameshift mutation (1637delC) in the FCN3 gene was recently shown to be associated with pyogenic infections mainly in the lungs.Objective: The aim of the study was to thoroughly evaluate the clinical findings of previously defined MBL deficient cohort in relation to their MBL2 and FCN3 genotypes. Methods:A total of 120 adult individuals previously defined as MBL deficient (≤500 ng/ml) were genotyped for variants in the MBL2 gene and for the 1637delC allele in the FCN3 gene. They answered detailed questionnaire focused on pulmonary and gastrointestinal infections. For comparison, 63 adult individuals were randomly selected from the general population and served as control subjects. Results:In the MBLD cohort the prevalence of genotypes A/A, A/O and O/O was 14.2%, 71.2%, and 14.2%, respectively. Thus, 85% carried the dysfunctional allele O. The MBLD cohort was significantly more prone to a variety of recurrent and severe infections than the control cohort. O/O individuals were more susceptible to oesophagitis and gastritis and had undergone gastroscopy significantly more often than A/A an A/O. Prevalence of heterozygosity (C/-) for the 1637delC allele was 4.2%. Conclusion IntroductionComplement activation is a first-line innate defence against invading pathogens. Activation of complements via the lectin pathway (LP) is mediated by five separate soluble serum pattern recognition proteins (PRP). These are mannan-binding lectin (MBL), collectin-11 (CL-11), ficolin-1 (M-ficolin), ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin) [1][2][3][4][5]. The LP-PRPs circulate in serum complexed with specific proteases named MASPs (MBL associated serine proteases; MASP-1, MASP-2 and MASP-3), and upon binding to pathogen associated sugar patterns the MASPs become activated and initiate the complement cascade leading to membranolytic attack and opsonophagocytosis [6].The physiological role of MBL has been well studied whereas the role of ficolins and CL-11 is less well investigated. MBL has a significant role in a number of pathogenetic and homeostatic processes. It binds and eliminates (through complement activation) various microorganisms and altered self-components, including dying host cells (apoptotic/ necrotic), circulating immune complexes (CICs) and immunoglobulins (agactosylated IgG and certain forms of IgM and IgA) [7][8][9][10]. The MBL molecule itself can act as a...

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Section: Discussionsupporting

confidence: 91%

supporting

confidence: 91%

Section: Discussionsupporting

confidence: 67%

mentioning

confidence: 97%

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Mannan-Binding Lectin (MBL) Deficient Individuals with the O/O Genotype are Highly Susceptible to Gastrointestinal Diseases

Thorsteinsdottir¹

2014

J Clin Cell Immunol

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“…Single base mutations within exon 1 and several mutations in the promoter region of the MBL gene result in interindividual differences in serum MBL levels. MBL deficiency is generally defined as serum ＜500 ng/mL, but some groups have defined severe MBL deficiency as ＜50 ng/mL and partial MBL deficiency from 50 ng/mL up to 1000 ng/mL 17,[28][29][30] . As there is no unique definition of functional MBL deficiency and clinical relevance may vary in different diseases, MBL ＜778 ng/ mL was chosen for the differentiation in MBL-deficient and MBL-sufficient obesity in our study.…”

Section: Mannose-binding Lectin Deficiencymentioning

confidence: 99%

Mannose-Binding Lectin in Obesity with Different Degrees of Metabolic Syndrome Abnormalities: Association with Atherogenic and Metabolic Traits

Strack

Baessler

Wagner

et al. 2012

JAT

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Aim:In subjects with metabolic syndrome (MetS) endothelial dysfunction is a very consistent finding. Processes leading to endothelial dysfunction and atherosclerosis involve the altered control of subclinical inflammation by innate immune defenses that possibly include mannose-binding lectin (MBL). We investigated the associations of MBL with traits of MetS and early atherosclerosis in obese subjects before and after marked weight reduction. Results: MBL concentrations did not differ between healthy lean and severely obese subjects independently of the presence of metabolic abnormalities. In severely obese subjects there was no significant difference concerning the cardiovascular risk profile, apolipoproteins, inflammatory and metabolic parameters, and markers of endothelial dysfunction and atherosclerosis between subjects with functional MBL deficienct (MBL＜778 ng/mL) and MBL sufficient (MBL ≥ 778 ng/mL) obesity. Marked weight loss did not influence MBL levels. Conclusions: Our findings suggest that plasma levels of MBL did not differ between healthy lean and severely obese subjects. MBL did not affect cardiovascular risk factors, or markers of endothelial dysfunction and early atherosclerosis in severely obese patients before and after marked weight loss.

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Proteomic profiling of blood‐dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis‐induced inflammatory response

Mareš

Richtrova

Hricinova

et al. 2010

Proteomics Clinical Apps

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Clinical manifestation of mannose-binding lectin deficiency in adults independent of concomitant immunodeficiency

Cited by 19 publications

References 23 publications

Mannan-Binding Lectin (MBL) Deficient Individuals with the O/O Genotype are Highly Susceptible to Gastrointestinal Diseases

Mannan-Binding Lectin (MBL) Deficient Individuals with the O/O Genotype are Highly Susceptible to Gastrointestinal Diseases

Mannose-Binding Lectin in Obesity with Different Degrees of Metabolic Syndrome Abnormalities: Association with Atherogenic and Metabolic Traits

Proteomic profiling of blood‐dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis‐induced inflammatory response

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