Clinical Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2005; 11(44): 6988-6994
Published online Nov 28, 2005. doi: 10.3748/wjg.v11.i44.6988
Anti-Saccharomyces cerevisiae antibody titers are stable over time in Crohn’s patients and are not inducible in murine models of colitis
Stefan Müller, Maya Styner, Beatrice Seibold-Schmid, Beatrice Flogerzi, Michael Mähler, Astrid Konrad, Frank Seibold
Stefan Müller, Maya Styner, Beatrice Seibold-Schmid, Beatrice Flogerzi, Astrid Konrad, Frank Seibold, Division of Gastroenterology, Department of Clinical Research, University Hospital Bern
Michael Mähler, Central Animal Facility and Institute for Laboratory Animal Science, Medical School Hannover, Germany
Author contributions: All authors contributed equally to the work.
Supported by the Swiss National Science Foundation grant no SNSF 31-59031.99 to F. Seibold
Correspondence to: Professor Frank Seibold, University Hospital Bern, Department of Gastroenterology, Freiburgstr. 10, 3010 Bern, Switzerland.
Telephone: +41-31-6328025 Fax: +41-31-6323671
Received: March 11, 2005
Revised: June 26, 2005
Accepted: July 1, 2005
Published online: November 28, 2005

AIM: To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology.

MATERIALS AND METHODS: Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of up to 3 years (ΔIgG/A) was correlated with clinical parameters such as CD activity index (CDAI) and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS and IL-10 knock out) were compared to control animals with respect to ASCA titers after oral yeast exposure.

RESULTS: ASCA IgG and IgA titers are stable over time in CD and non-CD patients. Fistular disease was associated with a higher rate of ASCA IgA positivity (P = 0.014). Ileal disease was found to have a significant influence on the ΔIgG of ASCA (P = 0.032). There was no correlation found between ASCA positivity or ΔIgG/A and clinical parameters of CD: CDAI and CRP. In mice, neither healthy animals nor animals with DSS-induced or spontaneous colitis exhibited a marked increase in ASCA titers after high-dose yeast exposure. On the other hand, mice immunized intraperitoneally with mannan plus adjuvant showed a marked and significant increase in ASCA titers compared to adjuvant-only immunized controls (P = 0.014).

CONCLUSION: The propensity to produce ASCA in a subgroup of CD patients is largely genetically predetermined as evidenced by their stability and lack of correlation with clinical disease activity parameters. Furthermore, in animal models of colitis, mere oral exposure of mice to yeast does not lead to the induction of marked ASCA titers irrespective of concomitant colonic inflammation. Hence, environment may play only a minor role in inducing ASCA.

Keywords: Crohn’s disease, Anti-Saccharomyces cerevisiae antibodies, Colitis