Laboratory and clinical studies of inflammatory bowel disease

Inflammatory bowel disease (IBD) is the collective term for a group of chronic idiopathic conditions that affect the gastrointestinal tract. These cause significant long-term morbidity in both adults and children. The pathogenesis involves the gut mucosal immune system and genetic factors affect disease expression. Previous studies have shown that Smad7, a negative regulatory of transforming growth factor (TGF)-β, is expressed at high levels in IBD in gut mucosal biopsies and lamina propria mononuclear cells, preventing the anti-inflammatory effects of TGF-β. We confirm high Smad7 levels in IBD. This persists in lamina propria mononuclear cells ex-vivo. Tumour necrosis factor-α, but not interferon-γ or TGF-β, increases Smad7 in lamina propria mononuclear cells from normal gut mucosa. However, Smad7 mRNA levels are not significantly different in normal and IBD tissue. Clinical studies of IBD patients examine the use of non-invasive methods to assess chronic gut symptoms and disease activity. Faecal calprotectin, a neutrophil protein, is a marker of gut inflammation. Using a highly sensitive assay, faecal calprotection >50μg/g has 85% sensitivity for pathology in children with chronic gut symptoms, but is not specific for IBD. Calprotectin levels correlate with disease activity in ulcerative colitis, but not in Crohn’s disease. Ultrasound imaging of the colon and terminal ileum shows that increased bowel wall thickens is also a marker of disease activity in IBD, but superior mesenteric artery blood flow, measured by Doppler analysis, does not correlate with disease activity. These data define new roles for both calprotectin and ultrasonography in the assessment of children with chronic gut symptoms and IBD.