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Title: Postoperative Crohn's Disease : an examination of local immunologic and microbiological factors influencing disease recurrence
Author: Murugananthan, Aravinth Uthesan
ISNI:       0000 0004 7963 6799
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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After ileo-caecal resection for Crohn's disease, postoperative Crohn's disease (POCD) recurrence rates are high and focused on the ileum. High recurrence rates, responsiveness to antibiotics and the predilection for recurrence to favour the ileum are incompletely understood. Dendritic cells (DC) are well characterised in inflammatory bowel disease and health for their roles in tolerance and inflammatory responses, but studies have focused heavily on colonic DC. Hence DC data comparing ileum and colon in controls, as well as POCD is sparse. We hypothesised that the DC profiles in small and large intestine differ and in POCD this may predispose recurrence to favour the ileum. Myeloid and plasmacytoid DC lineages in small and large intestine of healthy control subjects as POCD were examined. Plasmacytoid DC in POCD expressed less TLR-2 and 4 and more CCR7 and 9 than controls. The degree of POCD recurrence correlated with Th1/Th17 cytokine profiles within the neoterminal ileum. Additionally the small intestine in controls and POCD had a more inflammatory DC cytokine profile than the large intestine. LPS altered the DC cytokine toward a more inflammatory response in controls but minimally in POCD small intestine. Modulation with probiotics in controls had more effect within the small intestine than in colonic DC in controls, with no benefit seen in POCD small intestine derived DC. The microbiota plays an important role in POCD. As with previous studies we noted a dysbiosis within inflamed mucosa at surgery. POCD recurrence also correlated with clinical risk factors recurrence and microbiota at the time of surgery as well as there being a dysbiosis in patients who develop endoscopic recurrence. In conclusion we have shown altered DC profiles in POCD, predisposing this area to recurrence. Microbiota at surgery correlates with predetermined risk factors for disease recurrence and dysbiosis is noted with increasing endoscopic recurrence.
Supervisor: Omar, Hafid ; Knight, Stella ; Arebi, Naila Sponsor: Three Cs
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral