Antibodies to Saccharomyces cerevisiae in Crohns 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.