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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

Anti-S. cerevisiae antibody levels in healthy control subjects and Crohn’s disease patients.(A) Anti-S. cerevisiae antibody level was increased in Crohn’s disease patients when compared to healthy controls (P < 0.0001). Scatter plots of these data with the median line are shown. (B) Crohn’s disease patients with the clinical phenotype B2 had higher anti-S. cerevisiae antibody levels than those with B1 (P < 0.01) and there was a tendency for Crohn’s disease patients with B3 to have higher levels than patients with B1 (P = 0.0516). (C) Correlation between anti-S. cerevisiae antibody levels and mannose-binding lectin concentrations in Crohn’s disease patients with B3 (P < 0.015, r = −0.72). The results are expressed in arbitrary units (AU).
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f2: Anti-S. cerevisiae antibody levels in healthy control subjects and Crohn’s disease patients.(A) Anti-S. cerevisiae antibody level was increased in Crohn’s disease patients when compared to healthy controls (P < 0.0001). Scatter plots of these data with the median line are shown. (B) Crohn’s disease patients with the clinical phenotype B2 had higher anti-S. cerevisiae antibody levels than those with B1 (P < 0.01) and there was a tendency for Crohn’s disease patients with B3 to have higher levels than patients with B1 (P = 0.0516). (C) Correlation between anti-S. cerevisiae antibody levels and mannose-binding lectin concentrations in Crohn’s disease patients with B3 (P < 0.015, r = −0.72). The results are expressed in arbitrary units (AU).

Mentions: Anti-S. cerevisiae antibody levels were significantly higher in Crohn’s disease patients compared to healthy controls (P < 0.0001) (Fig. 2A). Furthermore, anti-S. cerevisiae antibody levels were significantly elevated in Crohn’s disease patients with the B2 phenotype compared to patients with the B1 phenotype (P < 0.01) and there was also a tendency towards elevated anti-S. cerevisiae antibody levels in Crohn’s disease patients with the B3 phenotype (P = 0.0516) (Fig. 2B). Mannose-binding lectin levels were inversely correlated with anti-S. cerevisiae antibody levels in Crohn’s disease patients with severe clinical phenotypes (P < 0.015, r = −0.72) (Fig. 2C).


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)

Anti-S. cerevisiae antibody levels in healthy control subjects and Crohn’s disease patients.(A) Anti-S. cerevisiae antibody level was increased in Crohn’s disease patients when compared to healthy controls (P < 0.0001). Scatter plots of these data with the median line are shown. (B) Crohn’s disease patients with the clinical phenotype B2 had higher anti-S. cerevisiae antibody levels than those with B1 (P < 0.01) and there was a tendency for Crohn’s disease patients with B3 to have higher levels than patients with B1 (P = 0.0516). (C) Correlation between anti-S. cerevisiae antibody levels and mannose-binding lectin concentrations in Crohn’s disease patients with B3 (P < 0.015, r = −0.72). The results are expressed in arbitrary units (AU).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Anti-S. cerevisiae antibody levels in healthy control subjects and Crohn’s disease patients.(A) Anti-S. cerevisiae antibody level was increased in Crohn’s disease patients when compared to healthy controls (P < 0.0001). Scatter plots of these data with the median line are shown. (B) Crohn’s disease patients with the clinical phenotype B2 had higher anti-S. cerevisiae antibody levels than those with B1 (P < 0.01) and there was a tendency for Crohn’s disease patients with B3 to have higher levels than patients with B1 (P = 0.0516). (C) Correlation between anti-S. cerevisiae antibody levels and mannose-binding lectin concentrations in Crohn’s disease patients with B3 (P < 0.015, r = −0.72). The results are expressed in arbitrary units (AU).
Mentions: Anti-S. cerevisiae antibody levels were significantly higher in Crohn’s disease patients compared to healthy controls (P < 0.0001) (Fig. 2A). Furthermore, anti-S. cerevisiae antibody levels were significantly elevated in Crohn’s disease patients with the B2 phenotype compared to patients with the B1 phenotype (P < 0.01) and there was also a tendency towards elevated anti-S. cerevisiae antibody levels in Crohn’s disease patients with the B3 phenotype (P = 0.0516) (Fig. 2B). Mannose-binding lectin levels were inversely correlated with anti-S. cerevisiae antibody levels in Crohn’s disease patients with severe clinical phenotypes (P < 0.015, r = −0.72) (Fig. 2C).

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