Evaluation of fecal and serum ASCA as predictors of relapse in patients suspected of having inflammatory bowel disease
Moman, Rajat N
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Background: Patients with Crohn disease (CD) or ulcerative colitis (UC) present with chronic inflammation and have a variety of complaints that can overlap with non-inflammatory gastrointestinal disorders. Non-invasive and inexpensive biomarkers can help elucidate the cause of a patient's symptoms. In addition, some biomarkers are thought to provide predictive value of disease activity. Data indicate that the non-specific biomarker, fecal lactoferrin (FLA), is helpful in diagnosis of gastrointestinal inflammation and is thought to have utility as a predictor of flare in patients with CD or UC. Data from other studies indicate that serum anti-Saccharomyces cerevisiae antibodies (ASCA) levels, while elevated in patients with CD, remains stable over time and are less useful for interval disease assessment. Data from an unpublished pilot study conducted at the Center for Inflammatory Bowel Diseases at Children's Hospital Boston suggests that fecal ASCA is elevated in patients with CD and may change over time. We now hypothesize that fecal ASCA may be a predictor of disease activity in patients with Inflammatory Bowel Disease (IBD). Methods: Stool samples were collected from 43 patients diagnosed with IBD, 27 diagnosed with CD, and 16 diagnosed with UC. Serum samples were collected from 39 patients diagnosed with IBD, 25 with CD, and 14 with UC. Only patients that were inactive for the previous three months before giving their sample were included. Data collected from patients that experienced a relapse of their disease within 12 months of giving their sample were compared to the group of patients that remained in remission. Each sample was tested for the level of FLA, as well as serum and fecal ASCA. Results: Seven of the 27 patients diagnosed with CD and six of the 16 patients diagnosed with UC experienced a flare within 12 months of providing their serum and stool samples. Patients with IBD that maintained remission had a median FLA level that was less than that observed in patients that went on to experience a clinical relapse, but this difference displayed borderline statistical significance (P-value of Wilcoxon test =0.06). The AUC-ROC for FLA was 0.67 and it had a sensitivity of 69% and specificity of 59%. The median fecal ASCA level observed in the group of patients that remained in clinical remission was less than that observed in the group of patients that went on to experience a clinical flare. The difference between the two groups was statistically significant (P-values of Wilcoxon test = 0.0016). The AUC-ROC for fecal ASCA was only 0.58 due to overlap between the two groups. The group of patients that remained in clinical remission had a median serum ASCA reading that was less than the group of patients that became active. The difference in serum ASCA readings between the two groups was statistically significant (P-values of Wilcoxon test = 0.0044); the AUC-ROC was 0.57. Conclusions: This study indicates that fecal ASCA may have utility as a predictive biomarker of disease activity in IBD. A future study will investigate fecal ASCA as a predictor of activity for patients specifically with Crohn disease.
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