Antibodies to saccharomyces cerevisiae in Crohn's disease: higher titers are associated with a greater frequency of mutant NOD2/CARD15 alleles and with a higher probability of complicated disease.
BACKGROUND
Both antibodies to Saccharomyces cerevisiae (ASCA) and carriage of two mutated NOD2/CARD15 alleles are associated with ileal Crohn's disease (CD) and complications requiring bowel surgery. We assessed the ASCA titer as a marker of CD clinical behavior.


METHODS
In a cross-sectional study, we phenotyped 117 unrelated CD patients. Titers (Units, U) of ASCA IgG and IgA were measured and patients were genotyped for three high-risk NOD2/CARD15 alleles. Multiple logistic regression and Cox regression analyses were used to assess the association of factors to CD phenotype and time to surgery.


RESULTS
ASCA seropositivity was associated with younger age at diagnosis, ileal disease, and complicated (stricturing or penetrating) behavior. There was a dose-response between the number of mutant NOD2/CARD15 alleles and the prevalence and titers of ASCA. The ASCA titer and tobacco use were associated with ileal disease independently of NOD2/CARD15 status. The ASCA titer (odds ratio (OR): 2.7 per 25 U, 95% confidence interval (CI): 1.5-46.7) and ileal disease were associated with stricturing/penetrating behavior, independently of NOD2/CARD15 status. Patients with ileal CD and ASCA titers of 41 U and 60 U needed 10 and 5 years of disease, respectively, to accumulate a 50% risk of complications.


CONCLUSIONS
ASCA+ patients had a greater frequency of mutant NOD2/CARD15 alleles. Nonetheless, higher ASCA titers were associated with higher probabilities of ileal CD and stricturing/penetrating behavior independently of NOD2/CARD15 status. Higher ASCA titers were associated with more rapid development of complications. This quantitative marker may prove useful in risk-stratifying patients to more aggressive antiinflammatory therapies.
Dassopoulos
Themistocles
T
Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Gastroenterology Division, Department of Medicine, Johns Hopkins University School of Medicine, 600 North Wolfe St., Blalock 463, Baltimore, MD 21287, USA. tdassopo@jhmi.edu
Frangakis
Constantine
C
Cruz-Correa
Marcia
M
Talor
Monica V
MV
Burek
C Lynne
CL
Datta
Lisa
L
Nouvet
Franklin
F
Bayless
Theodore M
TM
Brant
Steven R
SR
D000328:Adult; D000483:Alleles; D000908:Antibodies, Fungal / Q000097:blood*; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000276:immunology*
D000908:Antibodies, Fungal; D053473:Nod2 Signaling Adaptor Protein