Low Mannan-binding lectin serum levels are associated with complicated Crohn's disease and reactivity to oligomannan (ASCA)

Am J Gastroenterol. 2009 Oct;104(10):2508-16. doi: 10.1038/ajg.2009.315. Epub 2009 Jun 16.

Abstract

Objectives: Mannan-binding lectin (MBL) acts as a pattern-recognition molecule directed against oligomannan, which is part of the cell wall of yeasts and various bacteria. We have previously shown an association between MBL deficiency and anti-Saccharomyces cerevisiae mannan antibody (ASCA) positivity. This study aims at evaluating whether MBL deficiency is associated with distinct Crohn's disease (CD) phenotypes.

Methods: Serum concentrations of MBL and ASCA were measured using ELISA (enzyme-linked immunosorbent assay) in 427 patients with CD, 70 with ulcerative colitis, and 76 healthy controls. CD phenotypes were grouped according to the Montreal Classification as follows: non-stricturing, non-penetrating (B1, n=182), stricturing (B2, n=113), penetrating (B3, n=67), and perianal disease (p, n=65). MBL was classified as deficient (<100 ng/ml), low (100-500 ng/ml), and normal (500 ng/ml).

Results: Mean MBL was lower in B2 and B3 CD patients (1,503+/-1,358 ng/ml) compared with that in B1 phenotypes (1,909+/-1,392 ng/ml, P=0.013). B2 and B3 patients more frequently had low or deficient MBL and ASCA positivity compared with B1 patients (P=0.004 and P<0.001). Mean MBL was lower in ASCA-positive CD patients (1,562+/-1,319 ng/ml) compared with that in ASCA-negative CD patients (1,871+/-1,320 ng/ml, P=0.038). In multivariate logistic regression modeling, low or deficient MBL was associated significantly with B1 (negative association), complicated disease (B2+B3), and ASCA. MBL levels did not correlate with disease duration.

Conclusions: Low or deficient MBL serum levels are significantly associated with complicated (stricturing and penetrating) CD phenotypes but are negatively associated with the non-stricturing, non-penetrating group. Furthermore, CD patients with low or deficient MBL are significantly more often ASCA positive, possibly reflecting delayed clearance of oligomannan-containing microorganisms by the innate immune system in the absence of MBL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Fungal / blood
  • Case-Control Studies
  • Chi-Square Distribution
  • Crohn Disease / blood*
  • Crohn Disease / complications*
  • Crohn Disease / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Logistic Models
  • Male
  • Mannans / blood*
  • Mannose-Binding Lectin / blood
  • Mannose-Binding Lectin / deficiency*
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Saccharomyces cerevisiae / immunology
  • Schweiz

Substances

  • Antibodies, Fungal
  • Mannans
  • Mannose-Binding Lectin