Digestive Diseases and Sciences

, Volume 54, Issue 1, pp 103–110 | Cite as

The Relationship Between Virulence Factors of Helicobacter pylori and Severity of Gastritis in Infected Patients

  • Hasan Umit
  • Ahmet Tezel
  • Sebnem Bukavaz
  • Gulbin Unsal
  • Muserref Otkun
  • Ali Riza Soylu
  • Dilek Tucer
  • Metin Otkun
  • Selcuk Bilgi
Original Paper

Abstract

The outcome of Helicobacter pylori infection has been related to specific virulence-associated bacterial genotypes. The best known genotypic virulence factors of H. pylori are cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA). The objective of this study was to assess the relationship between H. pylori cagA and vacA status and histopathological findings. Esophagogastrodoedonoscopy was performed in 80 dyspeptic patients. Antrum and corpus biopsies were obtained for isolation of H. pylori and for histopathological assessment. The polymerase chain reaction was used to detect cagA and vacA genes of H. pylori using specific primers. Biopsy samples were stained with hematoxylin and eosin, and histopathological findings were graded using the “updated Sydney system”. H. pylori from 57 of the 80 patients was incubated. Of the 57 patients, 44 were cagA positive. In the corpus biopsy specimens there was a significant relationship between the density of H. pylori colonization (P = 0.02) and chronic inflammation (P = 0.02) and cagA-positive genotypes. In the antrum specimens there was a significant relationship between cagA positivity and neutrophil activity (P = 0.003) and glandular atrophy (P = 0.002), but not with H. pylori density, chronic inflammation, and intestinal metaplasia. The odds ratio of cagA-positive vs. cagA-negative strains for the presence of glandular atrophy, irrespective of grading and of gastric localization, was 4.62 (95% CI, 1.18–18.08, P = 0.041). No significant relationships were observed between vacA s1 and s2 genotypes and histopathological parameters. Corpus neutrophil infiltration was found to be more severe in the m1 group than in the m2 group (P = 0.004). Other histopathological features showed no difference between m1 and m2 genotypes. In conclusion H. pylori strains showing cagA positivity are associated with more severe gastritis in some histological features but virulence factors of H. pylori do not appear to determine the overall pattern of gastritis.

Keywords

Helicobacter pylori Gastritis Bacterial virulence factors cagA vacA 

References

  1. 1.
    Dunn BE, Cohen H, Blaser MJ (1997) Helicobacter pylori. Clin Microbiol Rev 10:720–741PubMedGoogle Scholar
  2. 2.
    Parsonnet J, Hansen S, Rodriguez L, Gelb AB, Warnke RA, Jellum E, Orentreich N, Vogelman JH, Friedman GD (1994) Helicobacter pylori infection and gastric lymphoma. N Engl J Med 330:1267–1271. doi:10.1056/NEJM199405053301803 PubMedCrossRefGoogle Scholar
  3. 3.
    Israel DA, Peek RM (2001) Pathogenesis of Helicobacter pylori-induced gastric inflammation. Aliment Pharmacol Ther 15:1271–1290. doi:10.1046/j.1365-2036.2001.01052.x PubMedCrossRefGoogle Scholar
  4. 4.
    McGee DJ, Mobley HLT (2000) Pathogenesis of Helicobacter pylori infection. Curr Opin Gastroenterol 16:24–31. doi:10.1097/00001574-200001000-00005 CrossRefGoogle Scholar
  5. 5.
    Jenks PJ, 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 43:752–758PubMedCrossRefGoogle Scholar
  6. 6.
    van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, Quint W (1998) Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology 115:58–66. doi:10.1016/S0016-5085(98)70365-8 PubMedCrossRefGoogle Scholar
  7. 7.
    Yamaoka Y, Souchek J, Odenbreit S, Haas R, Arnqvist A, Boren T, Kodama T, Osato MS, Gutierrez O, Kim JG, Graham DY (2002) Discrimination between cases of duodenal ulcer and gastritis on the basis of putative virulence factors of Helicobacter pylori. J Clin Microbiol 40:2244–2246. doi:10.1128/JCM.40.6.2244-2246.2002 PubMedCrossRefGoogle Scholar
  8. 8.
    Palli D, Menegatti M, Masala G, Ricci C, Saieva C, Holton J, Gatta L, Miglioli M, Vaira D (2002) Helicobacter pylori infection, anti-cagA antibodies and peptic ulcer: a case-control study in Italy. Aliment Pharmacol Ther 16:1015–1020. doi:10.1046/j.1365-2036.2002.01253.x PubMedCrossRefGoogle Scholar
  9. 9.
    Aydin F, Kaklikkaya N, Ozgur O, Cubukcu K, Kilic AO, Tosun I, Erturk M (2004) Distribution of vacA alleles and cagA status of Helicobacter pylori in peptic ulcer disease and non-ulcer dyspepsia. Clin Microbiol Infect 10:1102–1104. doi:10.1111/j.1469-0691.2004.00989.x PubMedCrossRefGoogle Scholar
  10. 10.
    Sezikli M, Guliter S, Apan TZ, Aksoy A, Keles H, Ozkurt ZN (2006) Frequencies of serum antibodies to Helicobacter pylori CagA and VacA in a Turkish population with various gastroduodenal diseases. Int J Clin Pract 60:1239–1243. doi:10.1111/j.1742-1241.2005.00778.x PubMedCrossRefGoogle Scholar
  11. 11.
    Ito Y, Azuma T, Ito S, Miyaji H, Hirai M, Yamazaki Y, Sato F, Kato T, Kohli Y, Kuriyama M (1997) Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol 35:1710–1714PubMedGoogle Scholar
  12. 12.
    van Doorn LJ, Figueiredo C, Sanna R, Pena S, Midolo P, Ng EK, Atherton JC, Blaser MJ, Quint WG (1998) Expanding allelic diversity of Helicobacter pylori vacA. J Clin Microbiol 36:2597–2603PubMedGoogle Scholar
  13. 13.
    Atherton JC, Cao P, Peek RM Jr, Tummuru MK, Blaser MJ, Cover TL (1995) Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 270:17771–17777. doi:10.1074/jbc.270.30.17771 PubMedCrossRefGoogle Scholar
  14. 14.
    Pagliaccia C, de Bernard M, Lupetti P, Ji X, Burroni D, Cover TL, Papini E, Rappuoli R, Telford JL, Reyrat JM (1998) The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc Natl Acad Sci USA 95:10212–10217. doi:10.1073/pnas.95.17.10212 PubMedCrossRefGoogle Scholar
  15. 15.
    Maeda S, Ogura K, Yoshida H, Kanai F, Ikenoue T, Kato N, Shiratori Y, Omata M (1998) Major virulence factors, VacA and CagA, are commonly positive in Helicobacter pylori isolates in Japan. Gut 42:338–343PubMedGoogle Scholar
  16. 16.
    Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham DY (1998) Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome. Helicobacter 3:241–253. doi:10.1046/j.1523-5378.1998.08056.x PubMedCrossRefGoogle Scholar
  17. 17.
    Erzin Y, Koksal V, Altun S, Dobrucali A, Aslan M, Erdamar S, Dirican A, Kocazeybek B (2006) Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA, babA2 genotypes, and correlation with clinical outcome in Turkish patients with dyspepsia. Helicobacter 11:574–580. doi:10.1111/j.1523-5378.2006.00461.x PubMedCrossRefGoogle Scholar
  18. 18.
    Dixon MF, Genta RM, Yardley JH, Correa P (1996) Classification and grading of gastritis. The updated Sydney system. International workshop on the histopathology of gastritis, Houston 1994. Am J Surg Pathol 20:1161–1181PubMedCrossRefGoogle Scholar
  19. 19.
    Spencer J, Wotherspoon AC (1997) Gastric MALT lymphoma and Helicobacter pylori. Cancer Surv 30:213–231PubMedGoogle Scholar
  20. 20.
    Graham DY (2000) Helicobacter pylori infection is the primary cause of gastric cancer. J Gastroenterol 35(Suppl 12):90–97PubMedGoogle Scholar
  21. 21.
    Demirturk L, Ozel AM, Yazgan Y, Solmazgul E, Yildirim S, Gultepe M, Gurbuz AK (2001) CagA status in dyspeptic patients with and without peptic ulcer disease in Turkey: association with histopathologic findings. Helicobacter 6:163–168. doi:10.1046/j.1523-5378.2001.00024.x PubMedCrossRefGoogle Scholar
  22. 22.
    Bulent K, Murat A, Esin A, Fatih K, MMMurat H, Hakan H, Melih K, Mehmet A, Bulent Y, Fatih H (2003) Association of CagA and VacA presence with ulcer and non-ulcer dyspepsia in a Turkish population. World J Gastroenterol 9:1580–1583PubMedGoogle Scholar
  23. 23.
    Saruc M, Demir MA, Kucukmetin N, Kandiloglu AR, Akarca US, Yuceyar H (2002) Histological and clinical predictive value of determination of tissue CagA status by PCR in Helicobacter pylori infected patients; results of the large population based study in western Turkey. Hepatogastroenterology 49:878–881PubMedGoogle Scholar
  24. 24.
    Malfertheiner P, Megraud F, O’Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ (2007) Current concepts in the management of Helicobacter pylori infection: the Maastricht III consensus report. Gut 56:772–781. doi:10.1136/gut.2006.101634 PubMedCrossRefGoogle Scholar
  25. 25.
    Malfertheiner P, Megraud F, O’Morain C, Hungin AP, Jones R, Axon A, Graham DY, Tytgat G (2002) Current concepts in the management of Helicobacter pylori infection–the Maastricht 2–2000 consensus report. Aliment Pharmacol Ther 16:167–180. doi:10.1046/j.1365-2036.2002.01169.x PubMedCrossRefGoogle Scholar
  26. 26.
    Beales IL, Crabtree JE, Scunes D, Covacci A, Calam J (1996) Antibodies to CagA protein are associated with gastric atrophy in Helicobacter pylori infection. Eur J Gastroenterol Hepatol 8:645–649PubMedGoogle Scholar
  27. 27.
    Warburton VJ, Everett S, Mapstone NP, Axon AT, Hawkey P, Dixon MF (1998) Clinical and histological associations of cagA and vacA genotypes in Helicobacter pylori gastritis. J Clin Pathol 51:55–61PubMedCrossRefGoogle Scholar
  28. 28.
    Atherton JC, Peek RM Jr, Tham KT, Cover TL, Blaser MJ (1997) Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology 112:92–99. doi:10.1016/S0016-5085(97)70223-3 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hasan Umit
    • 1
  • Ahmet Tezel
    • 1
  • Sebnem Bukavaz
    • 2
  • Gulbin Unsal
    • 1
  • Muserref Otkun
    • 2
  • Ali Riza Soylu
    • 1
  • Dilek Tucer
    • 1
  • Metin Otkun
    • 2
  • Selcuk Bilgi
    • 3
  1. 1.Department of GastroenterologyTrakya University Medical FacultyEdirneTurkey
  2. 2.Department of MicrobiologyTrakya University Medical FacultyEdirneTurkey
  3. 3.Department of PathologyTrakya University Medical FacultyEdirneTurkey

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