Clinical and molecular aspects of anti-TNF therapy in Crohn's disease

• Main Author: Sprakes, Michael Bramwell
• Published: University of Leeds 2015
• Subjects: 616.3
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.659181

INTRODUCTION: Crohn's disease (CD) is a, relapsing and remitting inflammatory disorder of the gastrointestinal tract. The pathogenesis of CD is not entirely understood, but may represent a combination of immune, genetic, and environmental stressors. Recently, a number of genes have been discovered that confer susceptibility to CD, many of these functioning in the innate immune system and novel therapies that act on molecules associated with the innate immune system are being developed. The anti-tumour necrosis factor (TNF) therapies, infliximab and adalimumab, are two such treatments, however data relating to the longer-term efficacy and safety of these therapies in CD, along with their cost implications, are limited. NLRP3 is a pathogen recognition receptor which, amongst other ligands, recognises muramyl dipeptide (MDP), the major ligand sensed by NOD2, the first susceptibility gene identified in CD. The NLRP3 inflammasome has recently been associated with inflammation in rheumatoid arthritis (RA) and has been shown to be modulated following infliximab therapy in this condition. AIMS: Firstly, to determine the long-term efficacy, safety and cost implications of anti-TNF therapies in CD, and also to assess the efficacy of switching to a second anti-TNF upon failure or non-response to the initial anti-TNF treatment. Secondly, to investigate the NLRP3 inflammasome and other associated inflammatory molecules in patients with CD at both gene and protein level to analyse if the NLRP3 inflammasome is modulated in CD patients compared to healthy controls, and to determine if the inflammasome is modified following treatment with the anti-TNF therapy, infliximab.