Helicobacter pylori and gastric lymphoma: high seroprevalence of CagA in diffuse large B-cell lymphoma but not in low-grade lymphoma of mucosa-associated lymphoid tissue type

Am J Gastroenterol. 2001 Aug;96(8):2324-8. doi: 10.1111/j.1572-0241.2001.04036.x.

Abstract

Objective: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is closely related to Helicobacter pylori (H. pylori) infection. In vitro studies have demonstrated H. pylori-induced B cell proliferation to be strain dependent. High prevalences of CagA protein and FldA protein have been reported in strains obtained from patients with gastric lymphoma of MALT type. The aims of the present study were to evaluate the prevalence of H. pylori infection and to search for antigenic particularities in 53 patients with primary gastric lymphoma in comparison with a group of infected patients with benign disease.

Methods: Of the 53 patients, 37 presented with low-grade lymphoma of MALT type (LGLM) and 16 with diffuse large B-cell lymphoma (DLBCL). They were compared to a group of 162 H. pylori-infected subjects comprising the control group: 111 had gastric or duodenal ulcer (GDU) and 51 nonulcer dyspepsia (NUD). Diagnosis of gastric lymphoma was established on histological examination of endoscopic specimens. Anti-H. pylori antibodies were assayed by third-generation ELISA. Western blot assay was used to detect antibodies against nine antigens (including CagA protein), which were recognized on the basis of their molecular weight.

Results: Of the 53 patients with gastric lymphoma, 45 were H. pylori-positive (85%): of these, 25 (56.5%) had anti-CagA antibodies. The prevalence of H. pylori seropositivity was 78% (29/37) in LGLM and 100% (16/16) in DLBCL. The prevalence of CagA seropositivity in H. pylori-positive patients was 44.8% (13/29) and 75% (12/16), respectively (p < 0.05). In comparison, the seroprevalence of CagA was 77.4% (86/111) in GDU patients and 43.1% (22/53) in NUD patients. The prevalence of antibodies to other antigenic proteins detected with Helicoblot 2.0 (19.5kd, 30kd, 35kd, VacA, HSPb, Urease A, and Urease B) did not differ among the groups except for 35kd protein, which was significantly higher (p < 0.01) in GDU than in NUD and in LGLM (76.6% vs 49% and 46.7%).

Conclusion: These findings suggest that in patients who develop gastric lymphomas in response to H. pylori, virulent strains expressing CagA protein are preferentially associated with DLBCL.

MeSH terms

  • Analysis of Variance
  • Antigens, Bacterial*
  • Antineoplastic Agents / therapeutic use
  • Bacterial Proteins / blood*
  • Blotting, Western
  • Chi-Square Distribution
  • Female
  • Helicobacter Infections / blood*
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / epidemiology
  • Helicobacter pylori*
  • Humans
  • Lymphoma, B-Cell / blood
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / microbiology*
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell, Marginal Zone / drug therapy
  • Lymphoma, B-Cell, Marginal Zone / microbiology*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / microbiology*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Seroepidemiologic Studies
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / pathology

Substances

  • Antigens, Bacterial
  • Antineoplastic Agents
  • Bacterial Proteins
  • cagA protein, Helicobacter pylori