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Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) in Korean patients with Crohn's disease and its relationship to the disease clinical course

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Abstract

Backgrounds/Aims

The implications of anti-Saccharomyces cerevisiae antibody for the diagnosis and the clinical course of Crohn's disease have been reported in Western countries, but rarely in Korea with its very different environmental and genetic backgrounds. We aimed to evaluate whether anti-S. cerevisiae antibody expression is associated with diagnostic findings, stratified Vienna classification phenotypes, disease activity and clinical course in Korean patients with Crohn's disease.

Materials/Methods

One hundred and fifteen patients with Crohn's disease, diagnosed and treated between 1990 and 2004 at Severance Hospital, Yonsei University and followed for at least 2 years, were included in this study. Anti-S. cerevisiae antibody was detected by an indirect immunofluorescence assay using EUROIMMUN kits. Information collected during treatment included demography, Vienna classification phenotype, clinical manifestation, laboratory tests, treatment modality and surgery rate. Disease activity was measured monthly using the Harvey-Bradshaw index.

Results

The anti-S. cerevisiae antibody prevalence was 38.3% in Crohn's disease patients. There was no difference in anti-S. cerevisiae antibody expression between genders. The mean age at diagnosis was younger for the anti-S. cerevisiae antibody positive group than the negative group (25.3 years versus 29.7 years, p < 0.05). Clinical manifestations and laboratory tests at diagnosis did not differ between the groups. The anti-S. cerevisiae antibody positive group had increased fibrostenosis (B2) and penetration (B3) compared to negative group, as determined by the Vienna classification (75.0% versus 53.5%, p < 0.05). Anti-S. cerevisiae antibody positive patients were admitted to the hospital more frequently than anti-S. cerevisiae antibody negative patients (p < 0.05). The yearly cumulative Harvey-Bradshaw index score was higher in the anti-S. cerevisiae antibody positive group than in the negative group during the follow-up period (p < 0.05). In addition, steroid (72.7% versus 52.1%, p < 0.05) and immunosuppressive (45.5% versus 23.9%, p < 0.05) treatments were more frequently given to the anti-S. cerevisiae antibody positive group.

Conclusions

Our data demonstrate that anti-S. cerevisiae antibody positive Crohn's disease patients had a more severe clinical course and thus often required more aggressive medical treatment.

Introduction

Crohn's disease (CD) is a chronic inflammation of the alimentary tract anywhere between the mouth and anus. Inflammation in CD is often discontinuous along the longitudinal axis of the gut, though it may involve all layers from the mucosa to serosa. Genetic and environmental factors are believed to play a role in CD etiology and pathogenesis [1].

Environmental factors (especially dietary components) have long been suspected to play a role in CD pathogenesis. In the late 1980s, Main et al. [2] first described elevated anti-S. cerevisiae antibody (ASCA) levels in CD patient serum. These antibodies are directed against the phosphopeptidomannans found in the cell wall of baker's and brewer's yeast (S. cerevisiae). Expression of this marker antibody reflects a specific mucosal immune-mediated response [2], [3].

The ASCA frequency in CD patients ranges from 50 to 80% of total IgG and 30–50% of total IgA antibodies [2], [3], [4], [5], [6]. ASCA testing provides clinicians with an additional diagnostic tool to differentiate possible inflammatory bowel disease (IBD) or indeterminate colitis [6]. Several studies have investigated the clinical value of measuring ASCA in CD patients. These reports have associated ASCA with several disease features, such as small bowel disease, earlier age of onset, fibrostenosis and penetrating disease and aggressive disease requiring surgical treatment [4], [5]. On the other hand, other studies suggest that ASCA is independent of disease activity, operative treatment or response to medical treatments [3], [5], [6]. Thus, a relationship between ASCA expression and CD clinical course is controversial.

In the present study, we aimed to evaluate whether ASCA expression is associated with clinical findings at diagnosis, stratified Vienna classification phenotype, disease activity and clinical course in Korean CD patients.

Section snippets

Patients and CD diagnosis

One hundred and fifteen CD patients, tested for ASCA expression, diagnosed and treated from January 1990 to December 2004 at Severance Hospital, Yonsei University College of Medicine, Seoul Korea, and followed for at least 2 years, were enrolled in this study. An additional 45 healthy people were enrolled as controls. A CD diagnosis was established by endoscopic, radiological and histological findings based on Japanese criteria [7], [8].

Serum samples from patients and healthy controls were

Mean age and gender

The ASCA prevalence was 38.3% (44/115) among CD patients and 8.8% (4/45) among healthy controls. The mean follow-up duration among the CD patients was 54.5 months (range, 24–150). The mean follow-up duration was 54.7 months (range, 24–150) among ASCA positive patients and 54.4 months (range, 24–129) among ASCA negative patients. There was no difference in ASCA expression between genders. The mean age at diagnosis was younger for the ASCA positive group than the negative group (Table 1).

Clinical manifestations and laboratory findings

The most

Discussion

CD is a heterogeneous inflammatory disease manifesting with diverse clinical features. There are reports that serological markers (p-ANCA in ulcerative colitis and ASCA in CD) can assist in the diagnosis and estimation of an IBD's clinical course. ASCA might differentiate CD from other IBDs, predict disease location or predict complications prior to their appearance. In clinical practice, ASCA could be of significant value, but the results have not been consistent between studies.

Studies have

Conflict of interest statement

None declared.

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    • Mannose-binding lectin deficiency is not associated with Anti-Saccharomyces cerevisiae antibody in Korean Crohn's disease patients

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      Our results were in agreement with those of a large Hungarian cohort in which MBL deficiency was not associated with CD and was not predictive of clinical features. In our study, the frequency of ASCA positivity was 48.1%, which was similar to that of previous studies conducted in Korean CD patients, ranging from 38.3% to 49.4% [37–39]. ASCA positivity is associated with the clinical features of CD, which suggests that ASCA might be useful in clinical practice as a preclinical or prognostic marker.

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      In our study, both ASCA positivity (44.4%) and the mean ASCA IgG titer (25.43 ± 19.26 Units) were significantly higher in CD patients than ITB patients and healthy controls. The frequency of ASCA positivity was similar to that reported previously for Korean subjects [18, 19]. The sensitivity, specificity, PPV, and NPV of ASCA for the diagnosis of CD, in patients who suspected for CD or ITB based on clinical symptoms and colonoscopic findings, were 43%, 90.6%, 81.6% and 62.4%, respectively.

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