Immunopathological and Modulatory Effects of Cag A(+) Genotype on Gastric Mucosa, Inflammatory Response, Pepsinogens, and Gastrin-17 Secretion in Iraqi Patients infected with H. pylori

OBJECTIVE: To determine the immunopathological correlation between Cag A+ H. pylori-specific IgG; pepsinogen I&II (PI&PII); gastrin-17 (G-17); status of gastric and duodenal mucosa and inflammatory activities on different gastroduodenal disorders. METHODOLOGY: Eighty gastroduodenal biopsies were taken from patients with gastroduodenal disorders for histopathological evaluation and H. pylori diagnosis. Serum samples were used for evaluation of gastric hormones and detection of H. pylori-specific IgG antibodies. The tissue expression of H. pylori Cag A gene was detected by in situ hybridisation. RESULTS: H. pylori IgG antibodies were detected in (88.8%) of enrolled patients. According to Cag A gene expression, Significant difference (P value ˂ 0.05) was detected in levels of PG I; PGII, PG I/PG II among patients with gastric disorders. Serum G-17 level was negatively correlated with Cag A gene expression (P-value = 0.04). There was a significant correlation between H. pylori IgG and PG I; PG II; G-17. The current study revealed that corpus atrophic gastritis was diagnosed histologically with (5%) gastric ulcer cases; (3.75%) of duodenal ulcer cases; (3.75%) of duodenitis cases; (1.25%) of gastropathy cases and (8.75%) of gastritis cases. At the same time H. pylori gastritis diagnosed concurrently with (8.75%) of gastric ulcer cases; (11.25%) of duodenal ulcer cases; (17.5%) of gastropathy cases; (3.75%) of duodenitis cases and (2.5%) of prepyloric ulcer cases. A significant correlation was reported between the Immunopathological status of gastric mucosa and endoscopic mucosal finding among duodenal ulcer cases and gastritis cases only. A positive correlation was reported between serum levels of PGI; PGII; PGI/PGII; G-17; PMNs grade and Immunopathological status of the gastroduodenal mucosa of H. pylori Infected patients. A significant difference was reported in lymphocyte grades among gastric disorders without correlation with immunohistopathological changes in the mucosa (P-value = 0.002). A significant difference was reported in lymphocyte grades among different disorders according to H. pylori IgG. A significant difference was reported in serum level of PG I; PG II; PG I/PG II; G-17 according to PMN and lymphocyte grades (P-value ˂ 0.01). PMNs grades positively correlated with gastric Cag A expression; H. pylori IgG; PG II; G-17 levels. PG I; PG I/ PG II correlated with lymphocyte grades (P-value ˂ 0.05); while PGII has a negative correlation (P-value = 0.039). CONCLUSION: Endoscopic mucosal finding does not reflect exactly the actual immunopathological changes of gastric mucosa during H. pylori infection. Secretion of gastrin was not affected by the presence of Cag A in gastric tissue. Instead, the fluctuation in the hormone level appears to be due to the presence of H. pylori infection in gastric tissue. Gastric tissue infiltration with PMNs & lymphocytes inflammatory infiltrates has a direct effect on PGs and gastrin levels in serum of infected patients. The level of PG I; PG II; G-17 secretion correlated with the development of immune response against H. pylori and production of specific H. pylori IgG. Finally, H. pylori can modulate gastric secretions through Cag A dependent and independent pathways.