Helicobacter Pylori-oncogenic protein cytotoxin-associated gene A and assessment of CD14 and CD163 in duodenal ulcer and gastric cancer patients



  • Hasanain Ihsan Hadi Department of Biology, Faculty of Science, University of Kufa, Iraq
  • Ahmed Abduljabbar Jaloob Aljanaby Department of Biology, Faculty of Science, University of Kufa, Iraq


CD14, CD163, CagA, DU, GC, H.pylori


Nearly half of the world's population is infected with Helicobacter pylori (H.pylori). A duodenal ulcer or stomach cancer can be caused by the infection by this bacterium. The aim of this work is to assess the levels of CD14 and CD163 in H.Pylori-positive patients infected with duodenal ulcer (DU) and gastric cancer (GC) and determine the prevalence of Helicobacter Pylori-oncogenic protein cytotoxin-associated gene A strains (H.pylori-CagA).  This study included 89 individuals distributed as follows: 20 healthy individuals as controls and 69 patients infected with H. Pylori have been divided as follows: 27 patients infected with H.pylori only (H.Pylori+), 22 H.pylori+DU and 20 H.pylori+GC. H. Pylori-oncogenic protein cytotoxin-associated gene A strains (H-pylori-CagA) were diagnosed based on a qualitative reverse-phase Enzyme Immunoassay Technique. CD163 and CD14 were measured in all individuals' serum using the Enzyme-Linked Immunoassay (ELISA) test.  Out of 69 patients infected with H.pylori, there was one CagA strain in H.pylori+; two and five strains were recorded in H.pylori+DU and H.pylori+GC, respectively. CD14 and CD163 serum concentrations were significantly higher (P≤0.05) in H. pylori+, H. pylori+DU and H. pylori+GC than in controls. Conclusions: Patients with CagA strains infection are at risk of developing a duodenal ulcer and stomach cancer.


Download data is not yet available.


Alhasnawi, H.M.R, Aljanaby, A.A.J., 2022a. The immunological role of CD4 and CD8 in patients infected with Helicobacter pylori and stomach cancer. Gene Reports 26. 101500. https://doi.org/10.1016/j.genrep.2022.101500

Alhasnawi, H.M.R, Aljanaby, A.A.J., 2022b Evaluation of Galectin-3 and CD19 in Helicobacter pylori patients infected with stomach cancer. Gene Reports 26 (2022) 101520. https://doi.org/10.1016/j.genrep.2022.101520.

Alipour, M., 2020. Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer. Journal of gastrointestinal cancer, pp.1-8. doi.org/10.1007/s12029-020-00518-5

Aljanaby, A.A.J., Al-Faham, Q.M.H., Aljanaby, I.A.J. and Hasan, T.H., 2022a. Epidemiological study of Mycobacterium Tuberculosis in Baghdad Governorate, Iraq. Gene Reports, 26.101467. doi.org/10.1016/j.genrep.2021.101467

Aljanaby, A.A.J., Al-Faham, Q.M.H., Aljanaby, I.J., Hasan, H.H., 2020b. Immunological role of cluster of differentiation 56 and cluster of differentiation 19 in patients infected with mycobacterium tuberculosis in Iraq. Gene Reports, 26.101514. doi.org/10.1016/j.genrep.2022.101514

Amieva, M. and Peek Jr, R.M., 2016. Pathobiology of Helicobacter pylori–induced gastric cancer. Gastroenterology, 150(1), pp.64-78. doi: 10.1053/j.gastro.2015.09.004

Amieva, M.R. and El–Omar, E.M., 2008. Host-bacterial interactions in Helicobacter pylori infection. Gastroenterology, 134(1), pp.306-323. doi.org/10.1053/j.gastro.2007.11.009

Ansari, S. and Yamaoka, Y., 2020. Helicobacter pylori virulence factor cytotoxin-associated Gene A (CagA)-mediated gastric pathogenicity. International Journal of Molecular Sciences, 21(19), p.7430. doi: 10.3390/ijms21197430.

Azuma, T., 2004. Helicobacter pylori CagA protein variation associated with gastric cancer in Asia. Journal of gastroenterology, 39(2), pp.97-103. doi: 10.1007/s00535-003-1279-4

Chonwerawong, M. and Ferrero, R.L., 2017. Regulation and functions of inflammasome-mediated cytokines in Helicobacter pylori infection. Microbes and infection, 19(9-10), pp.449-458. doi: 10.1016/j.micinf.2017.06.005

Cook, K.W., Letley, D.P., Ingram, R.J., Staples, E., Skjoldmose, H., Atherton, J.C. and Robinson, K., 2014. CCL20/CCR6-mediated migration of regulatory T cells to the Helicobacter pylori-infected human gastric mucosa. Gut, 63(10), pp.1550-1559. . doi.org/10.1136/gutjnl-2013-306253

Eslami, M., Yousefi, B., Kokhaei, P., Arabkari, V. and Ghasemian, A., 2019. Current information on the association of Helicobacter pylori with autophagy and gastric cancer. Journal of cellular physiology, 234(9), pp.14800-14811. doi.org/10.1002/jcp.28279

Etzerodt, A. and Moestrup, S.K., 2013. CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxidants & redox signaling, 18(17), pp.2352-2363. DOI: 10.1089/ars.2012.4834

Fehlings, M., Drobbe, L., Moos, V., Renner Viveros, P., Hagen, J., Beigier-Bompadre, M., Pang, E., Belogolova, E., Churin, Y., Schneider, T. and Meyer, T.F., 2012. Comparative analysis of the interaction of Helicobacter pylori with human dendritic cells, macrophages, and monocytes. Infection and immunity, 80(8), pp.2724-2734. DOI: 10.1128/IAI.00381-12

Ford, A.C., Yuan, Y. and Moayyedi, P., 2020. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Gut, 69(12), pp.2113-2121. doi: 10.1136/gutjnl-2020-320839

Hasan, T.H., Alasedi, K.K. and Aljanaby, A.A.J., 2021. A Comparative Study of Prevalence Antimicrobials Resistance Klebsiella pneumoniae among Different Pathogenic Bacteria Isolated from Patients with Urinary Tract Infection in Al-Najaf City, Iraq. Latin American Journal of Pharmacy, 40 (special issue): 174-8. http://www.latamjpharm.org/previous_issue.php?vol=0&num=1

Hatakeyama, M., 2014. Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis. Cell host & microbe, 15(3), pp.306-316. 10.1016/j.chom.2014.02.008

Hobsley, M., Tovey, F.I. and Holton, J., 2008. Controversies in the Helicobacter pylori/duodenal ulcer story. Transactions of the Royal Society of Tropical Medicine and Hygiene, 102(12), pp.1171-1175. doi:10.1016/j.trstmh.2008.04.035

Hou, J., Wang, X., Zhang, M., Wang, M., Gao, P. and Jiang, Y., 2019. Circulating CD14+ CD163+ CD209+ M2-like monocytes are associated with the severity of infection in Helicobacter pylori-positive patients. Molecular immunology, 108, pp.13-22. doi.org/10.1016/j.molimm.2019.01.017

Jolaiya, T.F., Fowora, M.A., Onyekwere, C., Ugiagbe, R., Agbo, I.I., Lesi, O., Ndububa, D.A., Adekanle, O., Njom, H.A., Idowu, A. and Adeleye, I.A., 2020. Duodenal ulcer promoting gene (DupA), plasticity region genes and sigma factors in H. pyloristrains from Nigeria. The Journal of Infection in Developing Countries, 14(02), pp.162-168. doi: 10.3855/jidc.11746

Lee, K.E., Khoi, P.N., Xia, Y., Park, J.S., Joo, Y.E., Kim, K.K., Choi, S.Y. and Do Jung, Y., 2013. Helicobacter pylori and interleukin-8 in gastric cancer. World Journal of Gastroenterology: WJG, 19(45), p.8192. doi: 10.3748/wjg.v19.i45.8192

Lee, Y.C., Chiang, T.H., Chou, C.K., Tu, Y.K., Liao, W.C., Wu, M.S. and Graham, D.Y., 2016. Association between Helicobacter pylori eradication and gastric cancer incidence: a systematic review and meta-analysis. Gastroenterology, 150 (5), pp.1113-1124. doi: 10.1053/j.gastro.2016.01.028

Lehours, P. and Robinson, K., 2020. Helicobacter, inflammation, immunology and vaccines. Helicobacter, 25, p.e12737. doi: 10.1111/hel.12737

Leja, M., Grinberga‐Derica, I., Bilgilier, C. and Steininger, C., 2019. Epidemiology of Helicobacter pylori infection. Helicobacter, 24, p.e12635. doi: 10.1111/hel.12635

Marshall, B.J., Armstrong, J.A., McGechie, D.B. and Clancy, R.J., 1985. Attempt to fulfil Koch's postulates for pyloric Campylobacter. Medical Journal of Australia, 142(8), pp.436-439. doi.org/10.5694/j.1326-5377.1985.tb113443.x

Michalkiewicz, J., Helmin-Basa, A., Grzywa, R., Czerwionka-Szaflarska, M., Szaflarska-Poplawska, A., Mierzwa, G., Marszalek, A., Bodnar, M., Nowak, M. and Dzierzanowska-Fangrat, K., 2015. Innate immunity components and cytokines in gastric mucosa in children with Helicobacter pylori infection. Mediators of inflammation, 2015. doi: 10.1155/2015/176726

Moyat, M., Mack, M., Bouzourene, H. and Velin, D., 2015. Role of inflammatory monocytes in vaccine-induced reduction of Helicobacter felis infection. Infection and immunity, 83(11), pp.4217-4228. doi.org/10.1128/IAI.01026-15

Myint, T., Miftahussurur, M., Vilaichone, R.K., Aye, T.T., Subsomwong, P., Uchida, T., Mahachai, V. and Yamaoka, Y., 2018. Characterizing Helicobacter pylori cagA in Myanmar. Gut and liver, 12(1), p.51. doi: 10.5009/gnl17053

Nguyen, T.H., Ho, T.T.M., Nguyen-Hoang, T.P., Qumar, S., Pham, T.T.D., Bui, Q.N., Bulach, D., Nguyen, T.V. and Rahman, M., 2021. The endemic Helicobacter pylori population in Southern Vietnam has both South East Asian and European origins. Gut pathogens, 13(1), pp.1-14. doi: 10.1186/s13099-021-00452-2

Nowińska, K. and Dzięgiel, P., 2010. Białka MCM i ich rola w proliferacji komórek i procesie nowotworowym The role of MCM proteins in cell proliferation and tumorigenesis. Postepy Hig Med Dosw (Online), 64, pp.627-635. doi: 10.3390/toxins10040163

Outlioua, A., Badre, W., Desterke, C., Echarki, Z., El Hammani, N., Rabhi, M., Riyad, M., Karkouri, M., Arnoult, D., Khalil, A. and Akarid, K., 2020. Gastric IL-1β, IL-8, and IL-17A expression in Moroccan patients infected with Helicobacter pylori may be a predictive signature of severe pathological stages. Cytokine, 126, p.154893. doi: 10.1016/j.cyto.2019.154893

Quiding-Järbrink, M., Raghavan, S. and Sundquist, M., 2010. Enhanced M1 macrophage polarization in human Helicobacter pylori-associated atrophic gastritis and in vaccinated mice. PloS one, 5(11), p.e15018. doi.org/10.1371/journal.pone.0015018.

Pachathundikandi, S.K., Blaser, N. and Backert, S., 2019. Mechanisms of inflammasome signaling, microRNA induction and resolution of inflammation by Helicobacter pylori. Molecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori, pp.267-302. doi: 10.1007/978-3-030-15138-6_11

Padra, M., Benktander, J., Robinson, K. and Lindén, S.K., 2019. Carbohydrate-dependent and antimicrobial peptide defence mechanisms against Helicobacter pylori infections. Molecular Mechanisms of Inflammation: Induction, Resolution and Escape by Helicobacter pylori, pp.179-207. https://link.springer.com/chapter/10.1007/978-3-030-15138-6_8

Pichon, M., Pichard, B., Barrioz, T., Plouzeau, C., Croquet, V., Fotsing, G., Chéron, A., Vuillemin, É., Wangermez, M., Haineaux, P.A. and Vasseur, P., 2020. Diagnostic accuracy of a noninvasive test for detection of Helicobacter pylori and resistance to clarithromycin in stool by the Amplidiag H. pylori+ ClariR real-time PCR assay. Journal of clinical microbiology, 58(4), pp.e01787-19. doi: 10.1128/JCM.01787-19

Polk, D.B. and Peek, R.M., 2010. Helicobacter pylori: gastric cancer and beyond. Nature reviews cancer, 10(6), pp.403-414.

Radziejewska, I., Leszczyńska, K. and Borzym-Kluczyk, M., 2014. Influence of monoclonal anti-Lewis b, anti-H type 1, and anti-sialyl Lewis x antibodies on binding of Helicobacter pylori to MUC1 mucin. Molecular and cellular biochemistry, 385(1), pp.249-255. doi: 10.1007/s11010-013-1833-1

Rashad, J.M.B.M., Aljanaby, A.A.J., 2021. Role of interleukin-2, interleukin-4 and cluster of differentiation-22 as an immune markers in individuals infected with Helicobacter pylori. J. Exp. Biol. Agric. Sci. 9 (3), 388–393. https://doi.org/10.18006/2021.9 (3).388.393.

Raza, Y., Ahmed, A., Khan, A., Chishti, A.A., Akhter, S.S., Mubarak, M., Bernstein, C., Zaitlin, B. and Kazmi, S.U., 2020. Helicobacter pylori severely reduces expression of DNA repair proteins PMS2 and ERCC1 in gastritis and gastric cancer. DNA repair, 89, p.102836. doi: 10.1016/j.dnarep.2020.102836.

Robinson, K. and Atherton, J.C., 2021. The Spectrum of Helicobacter-Mediated Diseases. Annual Review of Pathology: Mechanisms of Disease, 16, pp.123-144. doi.org/10.1146/annurev-pathol-032520- 024949

Rudnicka, K., Matusiak, A., Miszczyk, E., Rudnicka, W., Tenderenda, M. and Chmiela, M., 2013. Immunophenotype of peripheral blood natural killer cells and IL‐10 serum levels in relation to Helicobacter pylori status. Apmis, 121(9), pp.806-813. doi.org/10.1111/apm.12120

Saaed, H.K., Chiggiato, L., Webb, D.L., Rehnberg, A.S., Rubio, C.A., Befrits, R. and Hellström, P.M., 2021. Elevated gaseous luminal nitric oxide and circulating IL-8 as features of Helicobacter pylori-induced gastric inflammation. Upsala journal of medical sciences, 126. doi: 10.48101/ujms.v126.8116.

Saniee, P., Jalili, S., Ghadersoltani, P., Daliri, L. and Siavoshi, F., 2021. Individual hosts carry H. pylori isolates with different cagA features–motifs and copy number. Infection, Genetics and Evolution, p.104961. doi: 10.1016/j.meegid.2021.104961

Satomi, S., Yamakawa, A., Matsunaga, S., Masaki, R., Inagaki, T., Okuda, T., Suto, H., Ito, Y., Yamazaki, Y., Kuriyama, M. and Keida, Y., 2006. Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan. Journal of gastroenterology, 41(7), pp.668-673. doi: 10.1007/s00535-006-1838-6

Serena, S., Michele, R., Chiara, M., Gioacchino, L., Lorella, F., Tiziana, M., Gian, L.D.A. and Francesco, D.M., 2018. Relationship between Helicobacter pylori infection and GERD. Acta Bio Medica: Atenei Parmensis, 89(Suppl 8), p.40. doi: 10.23750/abm.v89i8-S.7918

Shetty, V., Lingadakai, R., Pai, G.C. and Ballal, M., 2021. Profile of Helicobacter pylori cagA & vacA genotypes and its association with the spectrum of gastroduodenal disease. Indian Journal of Medical Microbiology. doi: 10.1016/j.ijmmb.2021.06.001

Sugano, K., 2019. Effect of Helicobacter pylori eradication on the incidence of gastric cancer: a systematic review and meta-analysis. Gastric cancer, 22(3), pp.435-445. DOI: 10.1007/s10120-018-0876-0

Sukri, A., Hanafiah, A., Mohamad Zin, N. and Kosai, N.R., 2020. Epidemiology and role of Helicobacter pylori virulence factors in gastric cancer carcinogenesis. Apmis, 128(2), pp.150-161. doi: 10.1111/apm.13034

Sun, Y. and Zhang, J., 2019. Helicobacter pylori recrudescence and its influencing factors. Journal of cellular and molecular medicine, 23(12), pp.7919-7925. doi: 10.1111/jcmm.14682

Suyapoh, W., Tangkawattana, S., Suttiprapa, S., Punyapornwithaya, V., Tangkawattana, P. and Sripa, B., 2021. Synergistic effects of cagA+ Helicobacter pylori co-infected with Opisthorchis viverrini on hepatobiliary pathology in hamsters. Acta Tropica, 213, p.105740. doi: 10.1016/j.actatropica.2020.105740

Tohidpour, A., 2016. CagA-mediated pathogenesis of Helicobacter pylori. Microbial pathogenesis, 93, pp.44-55. doi: 10.1016/j.micpath.2016.01.005

Viala, J., Chaput, C., Boneca, I.G., Cardona, A., Girardin, S.E., Moran, A.P., Athman, R., Mémet, S., Huerre, M.R., Coyle, A.J. and DiStefano, P.S., 2004. Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nature immunology, 5(11), pp.1166-1174. doi.org/10.1038/ni1131

Vogelmann, R. and Amieva, M.R., 2007. The role of bacterial pathogens in cancer. Current opinion in microbiology, 10(1), pp.76-81. doi: 10.1016/j.mib.2006.12.004

Wang, H.P., Zhu, Y.L. and Shao, W., 2013. Role of Helicobacter pylori virulence factor cytotoxin-associated gene A in gastric mucosa-associated lymphoid tissue lymphoma. World journal of gastroenterology: WJG, 19(45), p.8219. doi: 10.3748/wjg.v19.i45.8219

Wang, F., Meng, W., Wang, B. and Qiao, L., 2014. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer letters, 345(2), pp.196-202. doi: 10.1016/j.canlet.2013.08.016

Wang, Y.K., Kuo, F.C., Liu, C.J., Wu, M.C., Shih, H.Y., Wang, S.S., Wu, J.Y., Kuo, C.H., Huang, Y.K. and Wu, D.C., 2015. Diagnosis of Helicobacter pylori infection: Current options and developments. World Journal of Gastroenterology: WJG, 21(40), p.11221. doi: 10.3748/wjg.v21.i40.11221

Waskito, L.A., Salama, N.R. and Yamaoka, Y., 2018. Pathogenesis of Helicobacter pylori infection. Helicobacter, 23, p.e12516. doi: 10.1111/hel.12516

White, J.R., Winter, J.A. and Robinson, K., 2015. Differential inflammatory response to Helicobacter pylori infection: etiology and clinical outcomes. Journal of inflammation research, 8, p.137. doi: 10.2147/JIR.S64888

Xu, S., Wu, X., Zhang, X., Chen, C., Chen, H. and She, F., 2020. CagA orchestrates eEF1A1 and PKCδ to induce interleukin-6 expression in Helicobacter pylori-infected gastric epithelial cells. Gut Pathogens, 12(1), pp.1-11. doi: 10.1186/s13099-020-00368-3. eCollection 2020.

Youssefi, M., Tafaghodi, M., Farsiani, H., Ghazvini, K. and Keikha, M., 2021. Helicobacter pylori infection and autoimmune diseases; Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. Journal of Microbiology, Immunology and Infection, 54(3), pp.359-369. doi: 10.1016/j.jmii.2020.08.011

Zhang, Q., Ding, J., Liu, J., Wang, W., Zhang, F., Wang, J. and Li, Y., 2016. Helicobacter pylori-infected MSCs acquire a pro-inflammatory phenotype and induce human gastric cancer migration by promoting EMT in gastric cancer cells. Oncology letters, 11(1), pp.449-457. doi: 10.3892/ol.2015.3897

Zhang, M., Ding, L., Wang, X., Hou, J., Li, M., Jiang, Y., He, X., Cui, M., Hu, F., Zhang, X. and Yang, J., 2018. Circulating CD14+ CD163+ CD115+ M2 monocytes are associated with the severity of new onset severe acute pancreatitis in Chinese patients. International immunopharmacology, 57, pp.181-189. doi: 10.1016/j.intimp.2018.02.018

Zhuang, Y., Cheng, P., Liu, X.F., Peng, L.S., Li, B.S., Wang, T.T., Chen, N., Li, W.H., Shi, Y., Chen, W. and Pang, K.C., 2015. A pro-inflammatory role for Th22 cells in Helicobacter pylori-associated gastritis. Gut, 64(9), pp.1368-1378. doi: 10.1136/gutjnl-2014-307020

Zhu, Q., Wu, X., Tang, M. and Wu, L., 2020. Observation of tumor-associated macrophages expression in gastric cancer and its clinical pathological relationship. Medicine, 99(17). doi: 10.1097/MD.0000000000019839



How to Cite

Hadi, H. I., & Aljanaby, A. A. J. (2022). Helicobacter Pylori-oncogenic protein cytotoxin-associated gene A and assessment of CD14 and CD163 in duodenal ulcer and gastric cancer patients. International Journal of Health Sciences, 6(S2), 839–851. https://doi.org/10.53730/ijhs.v6nS2.5134



Peer Review Articles