Duodenal ulcer promoting gene: effects on the pathophysiology of Helicobacter pylori infection and the host immune response

Ingram, Richard J.M. (2017) Duodenal ulcer promoting gene: effects on the pathophysiology of Helicobacter pylori infection and the host immune response. PhD thesis, University of Nottingham.

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Abstract

Duodenal ulceration remains a significant problem. Helicobacter pylori infection is the major cause of duodenal ulcers (DU). Worldwide, around 1 in 2 people are chronically colonised by H. pylori, most of whom will not develop gastroduodenal disease, though some will develop DU whilst others will develop gastric ulcer or gastric carcinoma. The risk of disease is related to bacterial virulence factors, host and environmental factors. Disease-specific bacterial risk factors have not been established.

Duodenal ulcer promoting gene (dupA) was proposed as a disease-specific bacterial virulence factor for DU. This study aims to examine the influence of dupA on clinical outcomes and whether these are epidemiologically consistent, if the dupA status of clinical isolates correlates with the key pathogenic features of DU in vivo, and if there is a biologically plausible role in disease through effects on host immune responses.

Results showed that the influence of dupA status on clinical outcomes was not specific to DU, but rather that epidemiological associations link dupA with an increased risk of gastroduodenal diseases in general for some populations. The dupA status of clinical isolates did not correlate with the key pathogenic features of DU in vivo, though there was some evidence of increased gastric mucosal inflammation in association with dupA+ strains. Experimental results using a human blood immune cell model show that monocyte-derived cells mediate a more pro-inflammatory response through interaction with the dupA system. This might be the mechanism that explains the in vivo associations of dupA with inflammation and disease.

In this study population, dupA did not satisfy the criteria of a true virulence factor that promotes duodenal ulceration. The assertion of this thesis is that dupA is misnamed.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Robinson, K.
Atherton, J.
Keywords: Helicobacter pylori; Duodenal ulcer promoting gene; dupA; Duodenal ulceration; Human mucosal immune response; Monocyte
Subjects: W Medicine and related subjects (NLM Classification) > WI Digestive system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 42105
Depositing User: Ingram, Richard
Date Deposited: 16 Oct 2017 14:30
Last Modified: 18 Oct 2017 01:33
URI: http://eprints.nottingham.ac.uk/id/eprint/42105

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