To examine the relationship between serum levels of anti-Saccharomyces cerevisiae antibodies (ASCAs) and intestinal permeability at a given time (hypothesis 1) and the probability of increased ASCA serum levels with increased intestinal permeability (hypothesis 2) in patients with Crohn's disease.Each hypothesis was tested retrospectively with its own study population: group A for hypothesis 1 and group B for hypothesis 2. Intestinal permeability was measured by lactulose/mannitol test and ASCAs were quantified by using ELISA. Patients received either no treatment or 5-aminosalicylates. The lactulose/mannitol test and sampling of sera for ASCA assessment had to be performed within 1 month in group A. In group B the highest intestinal permeability value obtained from among at least three measurements made during different stages of disease activity was chosen for evaluation.Both study populations consisted of 140 patients with Crohn's disease. Elevated IgG ASCAs were detected in 64% (90/140) in group A compared with 65% (91/140) in group B. In group A, 64% (90/140) and in group B 66% (92/140) were IgA ASCA positive. Correlation analysis showed a tendency for a positive relationship between IgG ASCAs and intestinal permeability in group A (tau = 0.16, P = 0.07) and in group B (tau = 0.16, P = 0.06). A positive trend was seen for the combination of high intestinal permeability and high IgG ASCAs in group B (chi-squared test, P = 0.07).Elevated serum levels of anti-S. cerevisiae antibodies do not seem to result primarily from a defect of the gut barrier. This observation points to an intrinsic pathomechanism in the development of increased ASCA serum levels.
OBJECTIVES: An increased prevalence of elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with Crohn's disease (CD) has been described. The aim of the present work was to investigate serum ASCA levels during the courses of prednisolone and mesalamine therapy in CD patients. METHODS: Serum samples of 25 patients with active CD were studied for ASCA levels before as well as 2 and 9 wk after initiation of a prednisolone tapering regimen. The influence of mesalamine (4 g o.d.) on serum ASCA levels compared to that of placebo was tested over 1 yr in 38 patients (20 mesalamine and 18 placebo) participating in a postoperative prophylaxis study. Serum IgG and IgA ASCA levels were measured by ELISA. Sera of 91 CD and 40 ulcerative colitis (UC) patients as well as 334 healthy donors were tested for ASCA to recalculate new cut-off values. RESULTS: For IgG ASCA cut-off values were determined to be 17.0 U and 25.0 U, and for IgA ASCA 9.3 U and 14.0 U. At baseline visit, 73.0% (46/63) of patients displayed serum ASCA positivity. During prednisolone therapy, a decrease in serum IgG and IgA ASCA levels from baseline to wk 2 (p < 0.0001 and p < 0.001, respectively) as well as to wk 9 (p < 0.001 and p= 0.01, respectively) was observed. A trend toward an association of ASCA positivity and steroid responsiveness was calculated (p= 0.07). During mesalamine treatment, no differences in changes of ASCA levels were observed compared to placebo at any time point. CONCLUSION: ASCA are stable markers during steroid and mesalamine treatment, highlighting their reliability for use in diagnosis of CD.
