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

Abstract

SUMMARYAnti-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.

NOD2/CARD15 Gene Polymorphisms in Crohn’s Disease: A Genotype-Phenotype Analysis in Danish and Portuguese Patients and Controls

“…No correlation between ASCA-positive patients and prevalence of mutation as previously shown in other studies was found [21, 23]. ANCA was positive among 7% (n = 4) of the Danish patients and 14% (n = 4) of the Portuguese patients.…”

“…Recently, Walker et al [21] and Klebl et al [39] have investigated associations between ASCA, disease phenotype and CARD15 genotype in CD patients. They found significantly lower values in patients with colonic disease compared to affection of the upper gastrointestinal tract and/or ileal involvement.…”

“…ASCAs are found in the blood in 50–80% of the patients with CD [21]. ANCA is an autoimmune antibody found in the blood in 50–70% of the patients with UC [22].…”

Serologic Markers in Inflammatory Bowel Disease

“…Mow et al (59 ) reported that 71.7% of CD patients with fibrostenosing disease had ASCAs vs 36.1% of patients without fibrostenosing disease and that 50.9% of patients with internal perforating disease had ASCAs vs 27.1% of patients without internal perforating disease. ASCAs have been associated with young age at diagnosis in several studies (40,41,52,58 ) but not in others (57 ).…”

“…ASCAs have been associated with stricturing as well as penetrating (56 -59 ) disease behavior and with ileal disease (small-bowel rather than colonic disease) (40,41,52,(57)(58)(59). For example, Quinton et al (41 ) reported that 70% of CD patients with small bowel involvement (with or without colonic disease) had ASCA antibodies vs 46% of the patients with pure colonic disease, and Walker et al (57 ) reported that 68% of patients with CD involving the ileum had ASCAs vs 38% of patients with colonic disease. Mow et al (59 ) reported that 71.7% of CD patients with fibrostenosing disease had ASCAs vs 36.1% of patients without fibrostenosing disease and that 50.9% of patients with internal perforating disease had ASCAs vs 27.1% of patients without internal perforating disease.…”