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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

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.
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Laura Choteau, Francis Vasseur, Frederic Lepretre, Martin Figeac, Corinne Gower, et al.. Polymorphisms in the Mannose-Binding Lectin Gene are Associated with Defective Mannose-Binding Lectin Functional Activity in Crohn's Disease Patients. Scientific Reports, Nature Publishing Group, 2016, 6, pp.29636. ⟨10.1038/srep29636⟩. ⟨hal-02513543⟩

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