Polymorphisms of the IL-1B and IL-1RN genes (which encode interleukin [IL]-1beta and IL-1 receptor antagonist, respectively) have been associated with hypochlorhydria and gastric cancer. We investigated the influence of bacterial virulence factors and host IL-1 polymorphisms on the development of histologic abnormalities in 210 Helicobacter pylori-infected patients with chronic gastritis. cagA(+)/vacAs1(+) H. pylori strains were associated with intestinal metaplasia (IM), atrophic gastritis (AG), and severe inflammation. Carriers of the proinflammatory IL-1B -511T/-31C and IL-1RN*2 alleles had an increased risk for the development of AG, IM, and severe inflammation, with odds ratios (ORs) of 1.7 (95% confidence interval [CI], 0.8-3.4) to 4.4 (95% CI, 1.5-12.9). The highest prevalence of severe gastric abnormalities was found in patients with both host and bacterial high-risk genotypes (cagA(+)/vacAs1(+)/IL-1B -511T/IL-1RN*2), with ORs of 24.8 (95% CI, 5.2-117.3) for severe lymphocytic infiltration, 9.5 (95% CI, 2.8-32.1) for severe granulocytic infiltration, 6.0 (95% CI, 2.4-15.5) for IM, and 2.4 (95% CI, 0.93-6.2) for AG. Combined bacterial/host genotyping thus may provide a clinical tool to identify patients at high risk of developing cancer.

Outer membrane proteins (OMPs) are incorporated into the outer plasma membrane of Helicobacter pylori and are important for, e.g., ion transport, adherence, structural and osmotic stability, and bacterial virulence but may also be antigenic due to their surface exposure. Previous proteome-based approaches with H. pylori lysates determined a strong serological reaction towards two H. pylori OMPs, HpaA (TIGR HP0797) and Omp18 (TIGR HP1125). PCR was used to detect DNA encoding the two proteins, and a positive signal was found in all H. pylori strains tested. Proteins were cloned and expressed in the human kidney cell line HK293 with the QiaExpressionist system with a C-terminal His tag. Only sera from infected persons showed a positive reaction with the recombinant proteins. Recombinant HpaA (rHpaA) and rOmp18 were incubated with human peripheral blood mononuclear cells and induced secretion of interleukin-12 (IL-12) and IL-10 from these cells. To determine the effect on antigen-presenting cells, human blood monocytic and dendritic cells (DCs) were isolated by magnetic cell separation. rOmp18 and rHpaA strongly stimulated major histocompatibility class II and CD83 expression 7-to 10-fold on isolated DCs. rHpaA and rOmp18 failed to stimulate IL-8 secretion from monocytes but increased secretion of IL-12 and IL-10 from DCs significantly. In summary, HpaA and Omp18 are recognized by human dendritic cells and induce their maturation as well as antigen presentation. HpaA and Omp18 of H. pylori thereby appear to have a specific antigenic potential in humans.

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