Abstract

BACKGROUND: Subgroups of patients with irritable bowel syndrome (IBS) may have low grade mucosal immune activity. Fecal calprotectin (f-calprotectin) levels are considered a marker for mucosal neutrophil inflammation and may be used as a biomarker for disease activity in inflammatory diseases. IBS patients are reported to have normal levels of calprotectin, but the levels may vary within the patient group, and it is not known whether this variation within or slightly above the normal range may reflect pathology or symptoms of the patients. AIM: To determine if levels of f-calprotectin may reflect the clinical and pathophysiological phenotype of IBS patients. METHODS: Analyses of f-calprotectin in stool samples of 98 IBS patients and 35 healthy controls were performed with Buhlmann ELISA (lower detection limit 10 ug/g). All IBS subjects completed the Bristol stool form (BSF) scale and the IBS symptom severity scale (IBS-SSS) questionnaire to assess gastrointestinal symptom severity. Patients also underwent a rectal barostat test with ballon distentions and colonic transit time measurement with ingestion of radiopaque rings. RESULTS: IBS patients had comparable levels of f-calprotectin to controls (17.5 (10-47.0) vs. 11(10-44.0) (median (2575%) percentiles) ug/g; p=0.21)). Among IBS patients, 13 subjects (13.2%) had f-calprotectin levels above the 90th percentile in the controls (98.8ug/g). There was no difference in IBS subgroup according to Rome III (IBS-C, IBS-D, IBS-M, IBS-U) in patients with high as compared to normal f-calprotectin. Also the disease duration was comparable in the two groups (9.5 (2-15) vs. 10 (5-15.3) years; p=0.46). There was no difference between IBS patients with high vs. normal levels of f-calprotectin regarding intensity or frequency of pain, bloating severity, bowel habit dissatisfaction, or daily life as estimated by IBS-SSS (Table 1). Also, total IBS-SSS score was comparable in the two groups (Table 1). The average stool form according to BSF (3.7 (2.9-4.4) vs. 4.1 (3.3-4.9); p=0.2) and stool frequency (1.5 (0.75-1.9) vs. 1.6 (1.2-2.3); p=0.29) were also similar in patients with high respective normal calprotectin levels. The pain threshold in rectal barostat test was comparable in IBS patients with high respective normal levels of f-calprotectin (24 (24-28) vs. 24 (20-32) mmHg; p=0.65). Moreover, oroanal transit time (OATT) was comparable in the two groups (1.5 (0.5-1.9) vs. 1.2(0.7-1.9) days; p=0.95) CONCLUSION: Fecal calprotectin within the normal range is not associated with the severity of IBS symptoms or key pathophysiological factors. Our data do not support that mucosal neutrophil inflammation is of major importance for symptom generation in IBS. Table 1. Symptom severity assessed by -IBS-SSS in IBS patients with high respective normal levels of fecal calprotectin.

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