Clinical Gastrointestinal Research
Our group conducts research in three areas related to inflammatory bowel disease (IBD).
Mucosal Immunity
The normal intestine is filled with immune cells, in this position they are ideally located and poised to act to prevent the entry of dangerous micro-organisms and food particles (antigens) into the body. Many researchers believe that an abnormal intestinal immune response underpins IBD. Our group has described the mucosal T cell receptor repertoire in infancy, and published research on the T cell receptor repertoire in IBD, demonstrating that specific subsets of T cells (groups of clones) are associated with disease.
For fifty years, glucocorticoids (steroids) have been one of the mainstay treatments in the management of IBD, however, 20-30% of IBD patients do not respond to steroid therapy. We are interested in the phenomenon of glucocorticoid resistance, and in addition to clinical trials (see below), we are currently investigating the impact of glucocorticoid therapy on the T cell repertoire in IBD (funded by NACC), and the interaction between steroids, the immune system and bone loss in IBD, in collaboration with Rheumatology (funded by P&G, and the David Telling Charitable Trust).
CD3 negative lymphocytes in the human infant intestine express surface membrane antigens of immature T cells. In the ileal tissue from a patient aged six days, CD3-7+ pre-T cells (blue) were observed in the lamina propria, and occasionally in the epithelium. Occasionally pre T cells were observed co-expressing CD5 and CD7 but without expression of CD3 CD16 or CD19 (arrowed). These cells are the phenotype of bone marrow derived precursors. Scale bars indicate 100m. For the orientation of villi and crypts, Lu indicates the luminal surface. Triple fluorescent-immunohistochemistry with FITC-conjugated CD3, CD16a and CD19 (green/yellow), Texas red-conjugated CD5 (CD3-5+, red) and AMCA-conjugated CD7 (CD3-7+, blue). (Williams, A.M., et al., Intestinal alpha beta T cells differentiate and rearrange antigen receptor genes in situ in the human infant. Journal of Immunology, 2004. 173(12): p. 7190-7199).
Novel Diagnostics
Many people have observed that faeces has a characteristic odour during gastrointestinal disease. Our group have characterised the profile of volatile organic compounds in gastrointestinal diseases – including IBD. The programme is rapidly expanding and now includes a range of diseases (funded by Wellcome Trust).
Two-dimensional plot of the showing the segregation of diseases based on profile of volatile compounds emitted from stool: asymptomatic volunteers (●), patients with Campylobacter jejuni (▲), patients with ulcerative colitis (□) and patients with Clostridium difficile (○) infections. (for further details see FASEB J 2007)
Clinical Trials
Our interest in glucocorticoid resistance in IBD has led to investigation of basiliximab in ulcerative colitis. Our group is collaborating with Dr C Dayan to take this to market (funded by Cerimon).
In addition, we have two other home-grown trials in collaboration with Dr J Tobias (Rheumatology) and Dr A Hawthorne, Cardiff, (both funded by P&G).
We are also actively involved in several commercial trials of novel agents in IBD.
Professor Chris Probert
Head of Clinical Gastrointestinal Research