Systemic IgG/IgA Balance and Antigen-Specific Seroreactivity as Predictors of the Topographic Distribution of Helicobacter pylori-Associated Gastritis

Background/Objectives: Helicobacter pylori infection induces a systemic humoral immune response that reflects both bacterial virulence and host immune regulation. While anti-H. pylori IgG is widely used as a marker of infection, its ability to predict the topographic distribution and biological activity of gastritis is limited. The objective of this study was to evaluate whether the relative predominance of systemic IgG versus IgA antibodies, IgG subclasses, and antigen-specific IgG reactivity could better reflect the features and topography of gastric inflammation. Methods: A total of 123 patients with dyspeptic symptoms, confirmed H. pylori infection, and histologically verified gastritis were included. Anti-H. pylori IgG and IgA levels were measured by ELISA, IgG1 and IgG2 subclasses by subclass-specific assays, and antigen-specific IgG reactivity (CagA, VacA, UreB66, 30 kDa, and UreA 26 kDa) by Western blot. Histopathological parameters of the antral and corpus mucosa were graded according to the updated Sydney system. Receiver operating characteristic (ROC) analysis and univariate and multivariate logistic regression were applied to identify predictors of gastritis topography. Results: Anti-H. pylori IgG levels correlated with the grade and activity of inflammation in the antrum, whereas IgA correlated with inflammatory parameters in the corpus. IgG1 and IgG2 showed limited associations with antral inflammatory activity. IgA showed the best diagnostic performance for pangastritis/corpus-predominant gastritis, while IgG2 best identified antrum-predominant gastritis. The combined serological profile defined as IgG > IgA together with 30 kDa antigen positivity was independently associated with antrum-predominant gastritis in multivariate analysis (OR 2.516; 95% CI 1.004–6.308). Conclusions: The systemic balance between IgG and IgA responses reflects the topographic distribution of H. pylori-associated gastritis. IgG predominance combined with 30 kDa antigen seropositivity represents an independent serological predictor of antrum-predominant gastritis and may improve non-invasive stratification of gastric inflammation.