© 2004 Blackwell Publishing Ltd, Helicobacter , 9, 158–164 158 Volume 9 • Number 2 • 2004 HELICOBACTER Blackwell Publishing, Ltd. The Functional Status of the Helicobacter pylori sabB Adhesin Gene as a Putative Marker for Disease Outcome Ramon de Jonge, *† Raymond G.J. Pot, * Ruud J.L.F. Loffeld, ‡ Arnoud H.M. van Vliet, * Ernst J. Kuipers * and Johannes G. Kusters * * Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Rotterdam, the Netherlands; † Department of Gastroenterology,VU University Medical Center, Amsterdam, the Netherlands; ‡ Department of Internal Medicine, de Heel Zaans Medical Center, Zaandam, the Netherlands ABSTRACT Background. Helicobacter pylori factors that contri- bute to disease outcome are largely unknown, but intimate contact with host cells mediated by outer membrane proteins is thought to play an important role. Expression of the outer membrane proteins OipA, HopZ, SabA, and SabB is regulated by phase- variable dinucleotide repeats in the coding regions of the respective genes. We have evaluated the correla- tion between the expression status of these four genes and disease outcome of H. pylori infection in a Dutch patient population. Materials and Methods. H. pylori strains, isolated from 96 Dutch patients with gastritis (n = 29), duodenal ulcer (n = 28), gastric ulcer (n = 21), gastric carcinoma (n = 9), and lymphoma (n = 9), were analyzed for the ‘on /off’ expression status of the H. pylori genes oipA, hopZ, sabA, and sabB by direct DNA sequence analysis of amplified fragments. Results. The off-status of sabB was significantly associated with duodenal ulcer ( p = .036), but not with gastric ulcer. In contrast, the expression status of oipA, hopZ, and sabA did not correlate with disease outcome. Furthermore, lymphoma strains appeared to express a significantly smaller amount of putative adhesins when compared to gastritis, gastric ulcer, duodenal ulcer and gastric carcinoma strains ( p < .02 for all groups tested). Conclusion. The off-status of sabB was found to be associated with duodenal ulcer disease, and thus represents a putative marker for disease outcome. Assum- ing that SabB is involved in bacterial adhesion, this association suggests that adherent H. pylori are more prone to elimination by the host immune system. Keywords. Helicobacter pylori, outer membrane protein, dinucleotide repeat, phase variation, duodenal ulcer, gastric cancer. C olonization of the human stomach by Heli- cobacter pylori is accompanied by chronic active gastritis, which can develop into peptic ulceration, adenocarcinoma of the distal stomach and mucus-associated lymphoid tissue (MALT) lymphoma [1]. Chronic H. pylori gastritis is ini- tiated by close contact of the bacterium with the epithelial surface [1,2]. Such contact is beneficial as it prevents removal by mucosal shedding and gives access to nutrients derived from the dam- aged epithelium. However, intimate contact with the epithelial surface may also be disadvantageous, as it decreases the ability of H. pylori to escape from the host immune response. The expression of various bacterial outer membrane proteins is thought to play a role in contact with and bind- ing to the gastric epithelial cells [3]. To date, the best characterized H. pylori adhesin is the outer membrane protein BabA, which interacts with the Lewis b blood group antigen [4]. Expression of BabA facilitates colonization of H. pylori and enhances the innate immune response by increasing interleukin (IL)-8 pro- duction of epithelial cells [5]. Other proteins that play an important role in adhesion to gastric epithelial cells have been recently identified and include SabA, SabB [6], HopZ [7], and OipA [8]. If outer membrane protein expression plays a role in epithelial contact, it is likely to influence the severity of inflammation, and thus the dis- ease outcome of H. pylori colonization. Several studies have demonstrated that, upon intimate adhesion of H. pylori to gastric epithe- lial cells, the cag pathogenicity island plays an Reprint requests to: Johannes G. Kusters, Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, Dijkzigt L-459, Dr Molewater- plein 40, 3015 GD Rotterdam, the Netherlands.