Impact of Helicobacter pylori CagA diversity on gastric mucosal damage: An immunohistochemical study of East-Asian-type CagA

Background and Aims: Recently, we successfully produced an anti-East-Asian-type CagA-specific antibody called alpha-EAS Ab, which is specifically immunoreactive only with East-Asian-type CagA but not Western-type CagA. In this study, the correlations between Helicobacter pylori CagA protein diversity and gastric mucosal condition was investigated using immunohistochemical staining with alpha-EAS Ab in Japan. Methods: There were 254 H. pylori-positive patients enrolled in this study. alpha-EAS Ab was used to determine the CagA phenotype instead of cagA sequencing, and, moreover, the histological findings and endoscopic gastric mucosal condition were evaluated according to the updated Sydney System and the Kimura-Takemoto classification system, respectively. Results: A total of 224 (88.2%) of the patients were immunoreactive for alpha-EAS Ab. The remaining 30 (11.8%) were negative for alpha-EAS Ab, suggesting that they were infected with either Western-type CagA or CagA-negative strains (i.e. non-East-Asian-type CagA strains). The grades of activity of gastritis, mucosal atrophy and intestinal metaplasia according to the updated Sydney System were significantly higher in patients infected with East-Asian-type CagA strains than those infected with non-East-Asian-type CagA strains. The grade of endoscopic gastric mucosal atrophy evaluated using the Kimura-Takemoto classification system was similar. All 28 strains isolated from patients with gastric cancer possessed the East-Asian-type CagA. Conclusions: Infection with East-Asian-type CagA H. pylori was more closely associated with gastric mucosal atrophy and gastric cancer than infection with non-East-Asian-type CagA H. pylori. The efficiency of immunohistochemical analysis for CagA should be equivalent to that of cagA sequencing.