Signal transducers and activators of transcription 3 signaling pathway: an essential mediator of inflammatory bowel disease and other forms of intestinal inflammation.

Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of chronic inflammatory bowel disease (IBD), are characterized by mucosal immune cell activation that is driven by a cytokine imbalance. Several cytokines involved in IBD act through the activation of the signal transducers and activators of transcription (STAT) family. We investigated the activation of STAT3 in the mucosa of CD and UC patients, and evaluated whether this event is specific for IBD patients. Using immunofluorescence and immunoblotting, total and phosphorylated STAT3 levels were assessed in biopsy specimens, isolated lamina propria mononuclear cells, and peripheral blood mononuclear cells from patients with CD, UC, other forms of intestinal inflammation, and control subjects. Immunoblotting revealed phosphorylated STAT3 in mucosal biopsy specimens from patients with CD, UC, celiac disease, and acute self-limited colitis, but not in the normal mucosa of control subjects. In IBD patients, STAT3 activation was confined to actively inflamed areas. Accordingly, activated STAT3 was detected in isolated lamina propria mononuclear cells from inflamed IBD tissues, but not in peripheral blood mononuclear cells from control subjects or IBD patients. Immunofluorescence demonstrated that the sources of activated STAT3 were macrophages and T lymphocytes, but not neutrophils. STAT3 activation also was detected in T cells infiltrating the duodenal mucosa of celiac disease patients. We conclude that STAT3 signaling occurs in both CD and UC, where it is strictly confined to areas of active inflammation and is limited to infiltrating macrophages and T cells. The occurrence of STAT3 signaling in other acute and chronic intestinal inflammatory conditions suggests that, rather than a specific feature of IBD, it represents a fundamental signaling pathway that is shared by multiple forms of gut inflammation.

Red cell distribution width as a marker of coeliac disease: a prospective study.

BACKGROUND: Coeliac disease is frequently underdiagnosed because of its protean presentations. Serological tests may be helpful in screening programmes for populations at risk, but they are costly. AIM: To determine prospectively whether a commonly available haematological test such as the red cell distribution width (RDW) could be of help in detecting unrecognized coeliac disease. METHODS: Of 353 consecutive adult patients referred to our outpatient malabsorption clinic, 198 in whom clinical suspicion was strong were referred for further investigations and intestinal biopsy. Seventy-six inflammatory bowel disease outpatients and 90 subjects admitted for diseases other than malabsorption were enrolled as the control group. RESULTS: RDW was increased in 94 (47.4%) and normal in 104 (52.5%) of 198 patients. Duodenal biopsy confirmed coeliac disease in 80 (85.1%) of the former patients and 69 (66.3%) of the latter patients. No correlation between RDW values and histological scores was found. Overall RDW increase was found in 80/149 (53.7%) patients with a definite diagnosis of coeliac disease, and in 14/49 (28.6%) patients in whom biopsy excluded the disease. A 1-year gluten withdrawal led to a significant decrease in RDW value, even in patients with obdurate mucosal impairment. CONCLUSIONS: In patients in whom there is a strong clinical suspicion of coeliac disease, an elevated RDW despite normal haemoglobin concentration may be a reliable predictor of the disease.