Immune and Molecular Alterations Associated with Helicobacter pylori Infection in Patients with Gastric Ulcer

Abstract

A gastric ulcer is a localised lesion in the stomach mucosa resulting from an imbalance between harmful factors and protective mechanisms. Infection with Helicobacter pylori (H. pylori) is a primary causative factor, as it triggers a chronic inflammatory response that leads to tissue damage. This study investigates changes in the expression of certain immune molecules and microRNAs (miRNAs) in patients with gastric ulcers and H. pylori infection, and evaluates their diagnostic potential. Materials and Methods: This study was conducted in Kirkuk city from November 2024 to September 2025and included 50 blood samples from patients with gastric ulcer (32 males and 18 females), in addition to 40 samples from healthy individuals as a control group. H. pylori infection was diagnosed using the rapid urease test (RUT), serological tests, and faecal antigen testing. The levels of  NLRP4 and CXCL12 in the serum were measured using the ELISA technique. The relative expression levels of miR-9, miR-362-5p, miR-502-5p and miR-650 were also determined using real-time quantitative polymerase chain reaction (qRT-PCR). Results: Diagnostic methods for H. pylori, including the rapid urease test (RUT), serological tests and faecal antigen testing, showed high positive rates among patients (82%, 78% and 76%, respectively). NLRP4 expression was significantly elevated in patients compared with healthy controls, with excellent diagnostic performance (AUC = 0.9965). CXCL12 levels were significantly lower in patients than in healthy controls. miRNA analysis revealed higher expression levels of miR-362-5p, miR-650, and miR-9 in patients compared with healthy controls, although these differences did not reach statistical significance. ROC analyses demonstrated diagnostic performance ranging from moderate to good. Meanwhile, miR-502-5p showed a trend toward reduced expression in patients with moderate diagnostic efficiency. Conclusion: H. pylori infection in patients with gastric ulcer is associated with a dysregulation of NOD-like receptors, particularly NLRP4, as well as certain microRNAs such as miR-9, miR-362-5p, and miR-650, reflecting a state of chronic inflammation and tissue damage. Some of these molecules, particularly NLRP4 and miR-650, may serve as promising biomarkers for diagnostic purposes. These findings underscore the complexity of host-pathogen interactions in the development of gastric ulcer and open avenues for exploring novel therapeutic and diagnostic strategies.