Abstract

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD; n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen–host cell interactions and responses, likely influencing the pathogenetic process.

Highlights

  • Autoimmune atrophic gastritis (AAG) is a relatively common form of gastritis [1] characterized by an immune response directed toward self-parietal cells [2]

  • The main steps of the study were: (1) the characterization of selected Toll-like receptors (TLR) polymorphisms associated with gastric cancer (GC), AAG and healthy donors (HD), (2) the association of discriminating TLR5 and TLR9 polymorphisms with serum level of pro-inflammatory H. pylori—induced Il-8 and IL-18 cytokines, with the serum gastrin G-17 and pepsinogen (PG)I for diagnosis of premalignant gastric lesions and risk factors for GC development (3)

  • The potential association of data obtained with the TLR5 and TLR9 polymorphisms

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Summary

Introduction

Autoimmune atrophic gastritis (AAG) is a relatively common form of gastritis [1] characterized by an immune response directed toward self-parietal cells [2]. In the late stages of the disease, an important reduction of the oxyntic glands accompanied by a reduction of the inflammatory reaction and the development of pseudo/hyperplastic polyps and/or intestinal metaplasia (IM) are present. Both the polyps and IM are associated with the development of gastric cancer (GC). A recent study, presenting limitations, reports an annual incidence of GC of about 1.4% in Americans with a biopsy-proven AAG on endoscopic gastric biopsy between January 2010 and November 2015; an incidence that was higher when compared with the estimated 0.07% annual-incidence of GC in the United States [3]

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