Helicobacter pylori infection, anti-cagA antibodies and peptic ulcer: a case–control study in Italy D. PALLI*, M. MENEGATTI  , G. MASALA*, C. RICCI  , C. SAIEVA*, J. HOLTON à , L. GATTA  , M. MIGLIOLI  & D. VAIRA   *Epidemiology Unit, CSPO, Florence, Italy;  Department of Internal Medicine and Gastroenterology, University of Bologna, Italy; àMicrobiology Department, University of London, London, UK Accepted for publication 27 January 2002 INTRODUCTION Helicobacter pylori infection has been consistently asso- ciated with a group of gastroduodenal conditions, including chronic atrophic gastritis, peptic ulcer, mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma. 1 Virulence factors involved in acid-stress protection (urease), vacuolating activity causing late endosome fusion (vacuolating cytotoxin gene, vacA), neutrophil activating protein (NAP) and superoxide dismutase activity have been described. 2, 3 Type I strains of H. pylori carry a pathogenicity island (named cag), of which cytotoxin associated gene A (cagA) is a marker, encoding a type IV secretion system and secreted effector substrates. Type II strains do not contain cag, or cag undergoes spontaneous excision. Type I strains have increased virulence and have also been strongly associated with certain clinical entities, such as duodenal ulcer and gastric cancer. The cagA antigen is an immunodominant antigen and is used for the evaluation of human immune responses. The SUMMARY Aim: To evaluate the association between infection with specific strains of Helicobacter pylori and peptic ulcer in patients referred for upper gastrointestinal endoscopy. Methods: One thousand, six hundred and twenty-six consecutive dyspeptic patients, referred to one Endoscopy Unit in Bologna, Italy, were enrolled. For each partici- pant, a blood sample was obtained for the measurement of distinct immunoglobulin G antibodies against H. pylori lysate and cytotoxin associated gene A (cagA). A case– control study included the whole series: patients diag- nosed with duodenal (n ¼ 275) or gastric (n ¼ 71) ulcer were identified and independently compared with con- trols with non-ulcer dyspepsia (n ¼ 1280). Results: H. pylori seroprevalence (at least one positive marker) was associated with increasing age, male sex and a diagnosis of peptic ulcer. This association was stronger with duodenal ulcer (multivariate odds ratio (OR), 5.2; 95% confidence interval (CI), 3.5–7.9) than with gastric ulcer (OR, 2.3; 95% CI, 1.2–4.4). Further analyses showed that H. pylori lysate+/cagA) subjects had a moderately increased risk of duodenal (OR, 3.2), but not gastric (OR, 1.1), ulcer. When cagA+ subjects were separately compared with seronegative patients, there was a six-fold increased risk for duodenal ulcer and a three-fold increased risk for gastric ulcer. Conclusions:A strong positive association between infection with a cagA+ H. pylori strain and the presence of peptic disease was found. The seroprevalence of anti-cagA antibodies among patients with non-ulcer dyspepsia is so high (41%) to preclude its use as a pre- endoscopic screening test. Ó 2002 Blackwell Science Ltd 1015 Correspondence to: Prof. D. Vaira, Department of Internal Medicine and Gastroenterology, University of Bologna, S. Orsola Hospital, Nuove Patologie, via Massarenti 9, 40138, Bologna, Italy. E-mail: vairadin@med.unibo.it Aliment Pharmacol Ther 2002; 16: 1015–1020.