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The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa

Kaneko, Kazuyo; Zaitoun, Abed M; Letley, Darren P; Rhead, Joanne L; Torres, Javier; Spendlove, Ian; Atherton, John C; Robinson, Karen

Authors

Kazuyo Kaneko

Abed M Zaitoun

Darren P Letley

Joanne L Rhead

Javier Torres

John C Atherton



Abstract

High-level expression of decay-accelerating factor, CD55, has previously been found in human gastric cancer (GC) and intestinal metaplasia (IM) tissues. Therapeutic effects of CD55 inhibition in cancer have been reported. However, the role of Helicobacter pylori infection and virulence factors in the induction of CD55 and its association with histological changes of the human gastric mucosa remain incompletely understood. We hypothesised that CD55 would be increased during infection with more virulent strains of H. pylori, and with more marked gastric mucosal pathology. RT-qPCR and immunohistochemical analyses of gastric biopsy samples from 42 H. pylori-infected and 42 uninfected patients revealed that CD55 mRNA and protein were significantly higher in the gastric antrum of H. pylori-infected patients, and this was associated with the presence of IM, but not atrophy, or inflammation. Increased gastric CD55 and IM were both linked with colonisation by vacA i1-type strains independently of cagA status, and in vitro studies using isogenic mutants of vacA confirmed the ability of VacA to induce CD55 and sCD55 in gastric epithelial cell lines. siRNA experiments to investigate the function of H. pylori-induced CD55 showed that CD55 knockdown in gastric epithelial cells partially reduced IL-8 secretion in response to H. pylori, but this was not due to modulation of bacterial adhesion or cytotoxicity. Finally, plasma samples taken from the same patients were analysed for the soluble form of CD55 (sCD55) by ELISA. sCD55 levels were not influenced by IM and did not correlate with gastric CD55 mRNA levels. These results suggest a new link between active vacA i1-type H. pylori, IM, and CD55, and identify CD55 as a molecule of potential interest in the management of IM as well as GC treatment. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Citation

Kaneko, K., Zaitoun, A. M., Letley, D. P., Rhead, J. L., Torres, J., Spendlove, I., …Robinson, K. (2022). The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa. Journal of Pathology, https://doi.org/10.1002/path.5990

Journal Article Type Article
Acceptance Date Jul 18, 2022
Online Publication Date Aug 18, 2022
Publication Date Aug 18, 2022
Deposit Date Sep 2, 2022
Publicly Available Date Sep 5, 2022
Journal Journal of Pathology
Print ISSN 0022-3417
Electronic ISSN 1096-9896
Publisher Wiley
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1002/path.5990
Keywords Pathology and Forensic Medicine
Public URL https://nottingham-repository.worktribe.com/output/10082809
Publisher URL https://onlinelibrary.wiley.com/doi/10.1002/path.5990

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