Anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease are associated with disease severity but not NOD2/CARD15 mutations

Abstract

Anti-Saccharomyces cerevisiae antibodies (ASCAs) have been proposed as serological markers, which may differentiate Crohn's disease (CD) from ulcerative colitis (UC) and predict disease phenotype. Their importance in pathogenesis is unproven. We investigated the relationship between ASCAs, disease phenotype and NOD2/CARD15 genotype in CD and whether ASCAs were related to antibodies to other fungal proteins. Serum from 228 patients [143 CD, 75 UC, 10 with indeterminate colitis (IC)] and 78 healthy controls (HC) were assayed for ASCA. Antibodies (IgA, IgG) to other fungal proteins (Fusarium species ATC20334, Mycoprotein) were measured in the same samples using an in-house enzyme-linked immunosorbent assay (ELISA) assay. ASCAs were present in 57% of CD, 19% of UC, 30% of IC and 8% of HCs. ASCA-positive status was a predictor for CD with sensitivity of 57%, specificity of 87%, positive predictive value of 78% and negative predictive value of 68%. ASCA was associated with proximal (gastroduodenal and small bowel involvement) rather than purely colonic disease (P < 0.001) and with a more severe disease phenotype and requirement for surgery over a median follow-up time of 9 years (P < 0.0001). No associations with NOD2/CARD15 mutations were seen. There was no association between ASCA and antibodies to MP (IgA or IgG). These data implicate ASCA as a specific marker of disease location and progression in CD, emphasizing the heterogeneity within IBD.

Fig. 1

ASCA as a disease marker. Column scatter plot of ASCA BI of patients in (a) all subject groups and (b) those with colonic CD, UC or IC. Dotted line denotes the ASCA BI cut-off value of 1. All values above the line are ASCA-positive. (a) Median ASCA BI: CD = 1·144, UC = 0·638, IC = 0·743, HC = 0·532. **ASCA BI of CD patients is significantly higher than all other groups (P < 0·001, Kruskal–Wallis). (b) Median ASCA BI: colonic CD = 0·824, UC = 0·638, IC = 0·743. *ASCA BI of colonic CD was significantly higher than that of UC or IC (P = 0·0031, Kruskal–Wallis).

Fig. 2

Antibody titres to mycoprotein. Column scatter graphs of MP antibody titres for IgA (a) and IgG (b) in the different subject groups. Small bars denote median values. Antibody titres are in arbitrary units. (a) Median MP IgA titres: CD = 754, IC = 118, UC = 72·5, HC = 132. **MP IgA titre was significantly higher in CD compared with other subject groups (P < 0·001, Kruskal–Wallis). (b) Median MP IgG titres: CD = 50·4, IC = 44·0, UC = 238, HC = 47·2. **MP IgG titre was significantly higher in UC compared with other subject groups (P < 0·001, Kruskal–Wallis).