The role of the CagA gene in the occurrence of the inflammatory response of the gastric mucosa in patients with chronic Helicobacter pylori-associated gastritis

  • S.V. Vernigorodskiy National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • D.S. Sukhan National Pirogov Memorial Medical University, Vinnytsya, Ukraine
Keywords: Helicobacter pylori, CagA, chronic gastritis, morphological changes


Currently, Helicobacter pylori infection (H. pylori) is recognized as one of the most important risk factors for gastrocarcinogenesis. It is known that this infection does not directly cause neoplastic changes in the gastric mucosa, and this is due to a number of consecutive events due to the long persistence of the pathogen in the human body. The initial stage of this cascade, of course, is the inflammatory response, due to the body’s ability to adapt to extraneous infection, which is the inevitable result of the interaction of H. pylori with cells of the gastric epithelium. This direct damaging effect is enhanced by the production of vacuolating cytotoxin and the release of products of the cytotoxin-associated CagA gene, which, at a pathomorphological level, is manifested by inflammatory infiltration of the gastric mucosa (GM) to some extent. On the relationship between the degree of contamination and the activity of the inflammation of the GM in people infected with the CagA strain, today there are different, often conflicting opinions, which is why in this work we set the goal of establishing the relationship between the nature of the inflammatory response and the presence of the CagA gene in H. pylori- infected patients. The purpose of the study is to determinate the relationship between the nature of the inflammatory response and the genetic features of the H. pylori strain (CagA genotype).We examined 365 patients, among whom 40 people were included in the control group (18 women and 22 men, whose average age was 45,33±15,46 and 42,82±12,31, respectively) without any gastroenterological pathology in the anamnesis , patients with chronic non-atrophic gastritis (188 people) and chronic atrophic gastritis (137 people). A close relationship was established between the presence of the CagA gene, activity and the degree of contamination for chronic non-atrophic gastritis: for a low degree of contamination, Fisher’s exact test was = 0.002, p<0.05, for a moderate degree - 0.012, p<0.05, for a high degree - 0,012, p<0.05. Accordingly, in chronic atrophic gastritis: for a low degree of contamination Fisher’s exact test = 0.011, p<0.05, for a moderate degree - 0.003, p<0.05, for a high degree - 0.001, p<0.05. There is also a close relationship between the degree of contamination and the activity of chronic gastritis: in patients with a high degree of contamination, CG activity was determined, as a rule, for stage 2-3. In our study, the inflammatory response depended on the presence or absence of the H. pylori strain in the patient, which contains the CagA genotype, which, in our opinion, plays a key role in triggering a cascade of inflammatory changes in the GM and progression of chronic gastritis.


[1] Aruin, L. I., Kapuller, L. L., & Isakov, V. A. (1998). Morphological diagnosis of diseases of the stomach and intestines. M.: “Triad-X”.
[2] Aruin, L. I., Kononov, A. V., & Mozgovoy, S. I. (2009). International classification of chronic gastritis: what should be accepted and what is in doubt. Archive of pathology, 4, 11-18.
[3] Bosman, F. T., Carneiro, F., Hruban, R. H., & Theise, N. D. (2010). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. IARC Press. Lyon, 417.
[4] Chukov, S. Z., & Pasechnikov, V. D. (2001). Do H. pylori virulence factors determine the nature of the gastroduodenal pathology? Russian Journal of Gastroenterology, Hepatology, Coloproctology, 11(2), 75-81.
[5] Dixon, M. F., Michael, D., & Path, F. R. (1996). Classification and Grading of Gastritis: The Updated Sydney System. The American Journal of Surgical Pathology, 20(10), 1161-1181.
[6] Evstigneev, I. V. (2011). Infection caused by Helicobacter pylori: state of the problem and prospects. Klіnіchna Іmunologіya. Allergology Infectology, 6-7, 14-19.
[7] Gaddy, J. A., Radin, J. N., Loh, J. T., Zhang, F., Washington, M. K., Peek, R. M., & Cover, T. L. (2013). High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis. Infection and Immunity, 81(6), 2258-2267. doi:10.1128/iai.01271-12.
[8] Ghasemi Basir, H. R., Ghobakhlou, M., Akbari, P., Dehghan, A., & Seif Rabiei, M. A. (2017). Correlation between the Intensity of Helicobacter pylori Colonization and Severity of Gastritis. Gastroenterology Research and Practice, 1-5. doi:10.1155/2017/8320496.
[9] Hatakeyama, M. (2014). Helicobacter pylori CagA and Gastric Cancer: A Paradigm for Hit-and-Run Carcinogenesis. Cell Host & Microbe, 15(3), 306-316. doi:10.1016/j.chom.2014.02.008.
[10] Isaeva, G. S., &Valiyeva, R. I. (2018). Biological properties and virulence of Helicobacter pylori. KMAH, 1 (20), 14-23.
[11] Iunusova, A. I., Litvinova, I. S., Karpeno, P. A., & Tohidpour, A. (2017). The Cytotoxin-Associated Gene A (CagA) of Helicobacter pylori: the Paradigm of an Oncogenic Virulence Factor. Journal of Siberian Federal University. Biology, 1-12. doi:10.17516/1997-1389-0015.
[12] Ivanova, N. L., Sokolova, I. L., Sadovnikova, V. V., & Smirnova, E. M. (2003). The activity of the inflammatory process in the gastric mucosa, depending on the degree of contamination of helicobacter pylori in children. Medikum, 3-4, 24-31.
[13] Jenks, P. J., Megraud, F., & Labigne, A. (1998). Clinical outcome after infection with Helicobacter pylori does not appear to be reliably predicted by the presence of any of the genes of the cag pathogenicity island. Gut, 43, 752-758.
[14] Kamogawa-Schifter, Y., Yamaoka, Y., Uchida, T., Beer, A., Tribl, B., Schöniger-Hekele, M., & Dolak, W. (2018). Prevalence of Helicobacter pylori and its CagA subtypes in gastric cancer and duodenal ulcer at an Austrian tertiary referral center over 25 years. PLOS ONE, 13(5), e0197695. doi:10.1371/journal.pone.0197695
[15] Kido, M., Tanaka, J., Aoki, N., Iwamoto, S., Nishiura, H., Chiba, T., & Watanabe, N. (2009). Helicobacter pylori Promotes the Production of Thymic Stromal Lymphopoietin by Gastric Epithelial Cells and Induces Dendritic Cell-Mediated Inflammatory Th2 Responses. Infection and Immunity, 78(1), 108-114. doi:10.1128/iai.00762-09
[16] Kononov, A. V. (2006). Inflammation as the basis of Helicobacter pylori – associated diseases. Archive of pathology, 5, 3-10.
[17] Kononov, A. V. (2009). Genetic regulation and phenotype of inflammation in Helicobacter pylori infection. Archive of pathology, 5, 57-63.
[18] Lee, J. Y., Kim, N., Choi, Y. J., Nam, R. H., Choi, Y. J., Kwon, Y. H., & Lee, D. H. (2014). Histologic Findings and Inflammatory Reactions After Long-term Colonization of Helicobacter felis in C57BL/6 Mice. Journal of Cancer Prevention, 19(3), 224-230. doi:10.15430/jcp.2014.19.3.224
[19] Maeda, S., Yoshida, H., Ikenoue, T., Ogura, K., Kanai, F., Kato, N. ... Omata, M. (1999). Structure of the cag pathogenicity island in Japanese Helicobacter pylori isolates. Gut, 44, 336-341.
[20] Medvetsky, Ye. B., & Vіlcanyuk, I. O. (2001). Method of staining Helicobacter pylori in cytological preparations. Reports of morphology, 7(1), 154-155.
[21] Morozov, I. A. (2000). Cytological diagnosis of Helicobacter pylori infection in the stomach. Russian Journal of Gastroenterology, Hepatology, Coloproctology, 2, 7-10.
[22] Mozgovoy, S. I., Novikov, D. G., & Kononov, A. V. (2010). Assessment of the integral indicator of mucosal atrophy in chronic gastritis in the prognosis of gastric cancer. Omsk Scientific Herald, 1, 81-83.
[23] Mozgovoy, S. I., Shimanskaya, A. G., & Osintseva, I. L. (2010). Russian revision of the international classification of chronic gastritis: evaluation of a new diagnostic approach using Capa-statistics methods. Omsk Scientific Herald, 1, 84-88.
[24] Nizhevich, A. A., Kuchina, E. S., & Akhmadeeva, E. N. (2012). The value of anti-CagA serological immune response in children with gastric ulcer and duodenal ulcer associated with helicobacter pylori. Basic research, 4(1), 212-215; URL:
[25] Nomura, S., Yamaguchi, H., Ogawa, M., Wang, T. C., Lee, J. R., & Goldenring, J. R. (2005). Alterations in gastric mucosal lineages induced by acute oxyntic atrophy in wild-type and gastrin-deficient mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 288(2), G362-G375. doi:10.1152/ajpgi.00160.2004.
[26] Park, J., Forman, D., Waskito, L., Yamaoka, Y., & Crabtree, J. (2018). Epidemiology of Helicobacter pylori and CagA-Positive Infections and Global Variations in Gastric Cancer. Toxins,10(4), 163. doi:10.3390/toxins10040163.
[27] Perwez Hussain, S., & Harris, C. C. (2007). Inflammation and cancer: An ancient link with novel potentials. International Journal of Cancer, 121(11), 2373-2380. doi:10.1002/ijc.23173
[28] Polyzos, S. A. (2017). Helicobacter pylori infection and esophageal adenocarcinoma: a review and a personal view. Annals of Gastroenterology. doi:10.20524/aog.2017.0213
[29] Potrokhova, E. A., Pomorgailo, E. G., & Kononov, A. V. (2012). Variants of the course of H. pylori-associated gastritis in adolescents after eradication of the pathogen. Russian Bulletin of Perinatology and Pediatrics, 2, 46-51.
[30] Schlemper, R., Riddell, R., & Kato, Y. (2000). Vienna classification of gastrointestinal epithelial neoplasia. Gut,47(2), 251-255.
[31] Slater, B. (1990). Superiorstain for Helicobacter pylori usingtoluidine. Journal of Clinical Pathology, 43(11), 961.
[32] Sugano, K., Tack, J., Kuipers, E. J., Graham, D. Y., El-Omar, E. M., Miura, S., & Malfertheiner, P. (2015). Kyoto global consensus report on Helicobacter pylorigastritis. Gut, 64(9), 1353-1367. doi:10.1136/gutjnl-2015-309252
[33] Suzuki, N., Murata-Kamiya, N., Yanagiya, K., Suda, W., Hattori, M., Kanda, H., & Hatakeyama, M. (2015). Mutual reinforcement of inflammation and carcinogenesis by the Helicobacter pylori CagA oncoprotein. Scientific Reports, 5(1). doi:10.1038/srep10024.
[34] Tegtmeyer, N., Wessler, S., & Backert, S. (2011). Role of the cag-pathogenicity island encoded type IV secretion system in Helicobacter pylori pathogenesis. FEBS Journal, 278(8), 1190–1202. doi:10.1111/j.1742-4658.2011.08035.x
[35] Tkach, S. M. (2009). H. pylori infection as a major cause of gastric carcinogenesis. Health of Ukraine, 1, 32-33.
[36] Tkach, S. M. (2016). Modern approaches to the classification, diagnosis and management of patients with chronic gastritis in the light of the international Kyoto consensus. Gastroenterologiya, 1, 110-116.
[37] Tsukamoto, T., Nakagawa, M., Kiriyama, Y., Toyoda, T., & Cao, X. (2017). Prevention of Gastric Cancer: Eradication of Helicobacter Pylori and Beyond. International Journal of Molecular Sciences, 18(8), 1699. doi:10.3390/ijms18081699
[38] Vieth, M., Dirshmid, K., Oehler, U., Helpap, B., von Luckner, A. G., & Stolte, M. (2001). Acute measles gastric infection. The American Journal of SurgicalPathology, 25(2), 259-62.
[39] Walduck, A., Schmitt, A., Lucas, B., Aebischer, T., & Meyer, T. F. (2004). Transcription profiling analysis of the mechanisms of vaccine-induced protection against H. pylori. The FASEB Journal, 18(15), 1955-1957. doi:10.1096/fj.04-2321fje.
[40] Yamaoka, Y., Kodama, T., Gutierrez, O., Kim, J. G., Kashima, K., & Graham, D. Y.(1999).Relationship between Helicobacter pylori iceA, cagA and vacA status and clinical outcome: studies in four different countries. Journal of Clinical Microbiology, 37(7), 2274-2279.
[41] Zhang, X.-Y., Zhang, P.-Y., & Aboul-Soud, M. A. M. (2016). From inflammation to gastric cancer: Role of Helicobacter pylori. Oncology Letters, 13(2), 543-548. doi:10.3892/ol.2016.5506.
[42] Zhang, Y., Pan, K., Zhang, L., Ma, J., Zhou, T., & Li, J. (2015). Helicobacter pylori, cyclooxygenase-2 and evolution of gastric lesions: results from an intervention trial in China. Carcinogenesis, bgv147. doi:10.1093/carcin/bgv147.
How to Cite
Vernigorodskiy, S., & Sukhan, D. (2018). The role of the CagA gene in the occurrence of the inflammatory response of the gastric mucosa in patients with chronic Helicobacter pylori-associated gastritis. Reports of Morphology, 24(3), 11-18.