Low Mannan-binding lectin serum levels are associated with complicated Crohn's disease and reactivity to oligomannan (ASCA).
OBJECTIVE
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.
Schoepfer
Alain M
AM
Department of Visceral Surgery and Medicine, Division of Gastroenterology, Inselspital, Bern University Hospital, Bern 3010, Switzerland.
Flogerzi
Beatrice
B
Seibold-Schmid
Beatrice
B
Schaffer
Thomas
T
Kun
Jürgen F J
JF
Pittet
Valerie
V
Mueller
Stefan
S
Seibold
Frank
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000908:Antibodies, Fungal / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000097:blood* / Q000150:complications* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008351:Mannans / Q000097:blood*; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency*; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000276:immunology; D013557:Switzerland
D000908:Antibodies, Fungal; D008351:Mannans; D037601:Mannose-Binding Lectin