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Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients.

Choteau L, Vasseur F, Lepretre F, Figeac M, Gower-Rousseau C, Dubuquoy L, Poulain D, Colombel JF, Sendid B, Jawhara S - Sci Rep (2016)

Bottom Line: Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms.The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients.This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U995, F-59000 Lille, France.

ABSTRACT
Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.

No MeSH data available.


Related in: MedlinePlus

Relationship between functional activity of the MBL-MASP complex and mannose-binding lectin concentration.(A) Mannose-binding lectin level was determined in 30 healthy control subjects and 69 Crohn’s disease patients. There was no significant difference between the two groups. (B) No significant difference was found between the concentration of mannose-binding lectin and clinical phenotype of Crohn’s disease. Scatter plots of these data with the median line are shown. Mannose-binding lectin concentration was determined in duplicate for each sample. (C) Functional activity of the MBL-MASP complex was determined in 30 healthy controls (open dot) and 69 Crohn’s disease patients (black dot). Data are the mean ± SD of two independent experiments. (D,E) Correlation between functional activity of the MBL-MASP complex and mannose-binding lectin concentration in 30 healthy controls (P < 0.0001, R = 0.8) and 69 Crohn’s disease patients (P < 0.0001, R = 0.75). AU, Arbitrary units.
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f1: Relationship between functional activity of the MBL-MASP complex and mannose-binding lectin concentration.(A) Mannose-binding lectin level was determined in 30 healthy control subjects and 69 Crohn’s disease patients. There was no significant difference between the two groups. (B) No significant difference was found between the concentration of mannose-binding lectin and clinical phenotype of Crohn’s disease. Scatter plots of these data with the median line are shown. Mannose-binding lectin concentration was determined in duplicate for each sample. (C) Functional activity of the MBL-MASP complex was determined in 30 healthy controls (open dot) and 69 Crohn’s disease patients (black dot). Data are the mean ± SD of two independent experiments. (D,E) Correlation between functional activity of the MBL-MASP complex and mannose-binding lectin concentration in 30 healthy controls (P < 0.0001, R = 0.8) and 69 Crohn’s disease patients (P < 0.0001, R = 0.75). AU, Arbitrary units.

Mentions: Serum concentrations of mannose-binding lectin were not statistically different between Crohn’s disease patients and healthy controls although a slightly elevated mannose-binding lectin level was observed in Crohn’s disease patients (P = 0.8). The concentration of mannose-binding lectin was not associated to the clinical phenotype of the disease (B1, B2, or B3) (Fig. 1A,B).


Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients.

Choteau L, Vasseur F, Lepretre F, Figeac M, Gower-Rousseau C, Dubuquoy L, Poulain D, Colombel JF, Sendid B, Jawhara S - Sci Rep (2016)

Relationship between functional activity of the MBL-MASP complex and mannose-binding lectin concentration.(A) Mannose-binding lectin level was determined in 30 healthy control subjects and 69 Crohn’s disease patients. There was no significant difference between the two groups. (B) No significant difference was found between the concentration of mannose-binding lectin and clinical phenotype of Crohn’s disease. Scatter plots of these data with the median line are shown. Mannose-binding lectin concentration was determined in duplicate for each sample. (C) Functional activity of the MBL-MASP complex was determined in 30 healthy controls (open dot) and 69 Crohn’s disease patients (black dot). Data are the mean ± SD of two independent experiments. (D,E) Correlation between functional activity of the MBL-MASP complex and mannose-binding lectin concentration in 30 healthy controls (P < 0.0001, R = 0.8) and 69 Crohn’s disease patients (P < 0.0001, R = 0.75). AU, Arbitrary units.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940739&req=5

f1: Relationship between functional activity of the MBL-MASP complex and mannose-binding lectin concentration.(A) Mannose-binding lectin level was determined in 30 healthy control subjects and 69 Crohn’s disease patients. There was no significant difference between the two groups. (B) No significant difference was found between the concentration of mannose-binding lectin and clinical phenotype of Crohn’s disease. Scatter plots of these data with the median line are shown. Mannose-binding lectin concentration was determined in duplicate for each sample. (C) Functional activity of the MBL-MASP complex was determined in 30 healthy controls (open dot) and 69 Crohn’s disease patients (black dot). Data are the mean ± SD of two independent experiments. (D,E) Correlation between functional activity of the MBL-MASP complex and mannose-binding lectin concentration in 30 healthy controls (P < 0.0001, R = 0.8) and 69 Crohn’s disease patients (P < 0.0001, R = 0.75). AU, Arbitrary units.
Mentions: Serum concentrations of mannose-binding lectin were not statistically different between Crohn’s disease patients and healthy controls although a slightly elevated mannose-binding lectin level was observed in Crohn’s disease patients (P = 0.8). The concentration of mannose-binding lectin was not associated to the clinical phenotype of the disease (B1, B2, or B3) (Fig. 1A,B).

Bottom Line: Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms.The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients.This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies.

View Article: PubMed Central - PubMed

Affiliation: INSERM, U995, F-59000 Lille, France.

ABSTRACT
Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn's disease and this deficiency is frequently associated with a severe Crohn's disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn's disease phenotype in 69 Crohn's disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin-mannose-associated serine protease (MBL-MASP) functional activity in Crohn's disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn's disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn's disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.

No MeSH data available.


Related in: MedlinePlus