Publications

@article{Kaneko2022-jg,

title = {The active form of Helicobacter pylori vacuolating cytotoxin 

 induces decay-accelerating factor CD55 in association with 

 intestinal metaplasia in the human gastric mucosa},

author = {Kazuyo Kaneko and Abed M Zaitoun and Darren P Letley and Joanne L Rhead and Javier Torres and Ian Spendlove and John C Atherton and Karen Robinson},

year  = {2022},

date = {2022-10-01},

journal = {J. Pathol.},

volume = {258},

number = {2},

pages = {199\textendash209},

publisher = {Wiley},

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.},

keywords = {CD55, decay-accelerating factor, gastric   cancer, Helicobacter pylori, intestinal metaplasia, vacuolating cytotoxin, virulence   factor},

pubstate = {published},

tppubtype = {article}

}