Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients.

One of the several possible causes of irritable bowel syndrome (IBS) is thought to be low-grade mucosal inflammation. Flagellin, the primary structural component of bacterial flagellae, was shown in inflammatory bowel disease patients to activate the innate and adaptive immunity. It has not yet been conclusively established if IBS patients show reactivity to luminal antigens. In 266 patients [112 IBS, 61 Crohn's disease (CD), 50 ulcerative colitis (UC) and 43 healthy controls (HC)], we measured antibodies to flagellin (FAB, types A4-Fla2 and Fla-X), anti-Saccharomyces cerevisiae antibodies (ASCA) (both ELISA), antipancreas antibodies (PAB) and perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) (both IF). All IBS patients had normal fecal calprotectin (mean 21 microg mL(-1), SD 6.6) and fulfilled the ROME II criteria. Frequencies of antibodies in patients with IBS, CD, UC and HC, respectively, are as follows (in per cent): antibodies against A4-Fla2: 29/48/8/7; antibodies against Fla-X: 26/52/10/7; ASCA: 6/59/0/2; p-ANCA: 0/10/52/0; and PAB: 0/28/0/0. Antibodies against A4-Fla2 and Fla-X were significantly more frequent in IBS patients than in HC (P = 0.004 and P = 0.009). Antibodies to A4-Fla2 and Fla-X were significantly more frequent in IBS patients with antecedent gastroenteritis compared to non-postinfectious IBS patients (P = 0.002 and P = 0.012). In contrast to ASCA, PAB and p-ANCA, antibodies against A4-Fla2 and Fla-X were found significantly more often in IBS patients, particularly in those with postinfectious IBS, compared to HC. This observation supports the concept that immune reactivity to luminal antigens has a putative role in the development of IBS, at least in a subset of patients.

Regional differences in L-selectin expression in murine intestinal lymphocytes.

BACKGROUND & AIMS: The expression of the lymphocyte homing receptor and activation marker L-selectin is different in colon and small intestinal intraepithelial lymphocytes (IELs). In this study, the mechanism of this difference in L-selectin expression was investigated. METHODS: L-selectin expression on lymphocytes was measured by flow cytometry. L-selectin messenger RNA (mRNA) was detected by reverse-transcription polymerase chain reaction. L-Selectin expression on peripheral lymphocytes was analyzed after incubation with cytokines, food and bacterial antigens, and homogenates of small and large bowel. RESULTS: L-selectin was expressed by none of the small intestinal IELs but by 30% of those in the colon and by 60% of splenocytes. mRNA for L-selectin was detectable in isolated lymphocytes of all three sites. L-Selectin was down-regulated in colon IELs during colitis and up-regulated in small intestinal IELs after in vitro culture for 48 hours. Incubation of splenocytes with small intestinal homogenates led to a rapid down-regulation of L-selectin (1% vs. 60% untreated). Preincubation with a metalloproteinase inhibitor prevented L-selectin loss. CONCLUSIONS: The mechanism of the differential expression of L-selectin in mouse small intestine and colon appears to be an increased functional activity of a metalloproteinase (sheddase) in the small intestine compared with the colon.