Genetic diversity in the Helicobacter pylori cag pathogenicity island and effect on expression of anti-CagA serum antibody in UK patients with dyspepsia

Aims-To investigate variation within the cag pathogenicity island (PAI) of Helicobacter pylori isolated from patients with dyspepsia in mid-Essex, and to evaluate the effect on expression of anti-CagA antibody. Methods-Sixty two isolates of H pylori cultured from gastric biopsies were screened by specific PCR assays for the presence of cagA and other gene mar kers (cagD and cagE, and virD4) in the cag PAI. An enzyme linked immunosorb ent assay (ELISA) kit (Viva Diagnostica helicobacter p120) was used to test for anti-CagA IgG antibody in matching sera. Isolates were also genotyped by vacuolating cytotoxin polymerase chain reaction (PCR) analysis, and test ed for absence of the complete cag PAI (empty site FCR assay). Results-Forty one of the H pylori isolates had a cag PAI containing cagA. O ne strain had no cagA but other cag PAI loci were present, whereas the rema ining 20 strains had no detectable cag PAI markers. Anti-CagA IgG antibody was detected in 34 sera by the ELISA assay, and when compared with the cag PAI genotype of the infecting strain, accuracy, sensitivity, and specificit y were 92%, 87%, and 100%, respectively. The seven discrepant or borderline strains in the ELISA were all vacA sl but differed in other genotypic mark ers. Conclusions-The cag PAI was widely distributed in H pylori from patients wi th dyspepsia in mid-Essex who had different gastric pathologies. Infection with a strain having an uninterrupted cag PAI was associated with the prese nce of anti-CagA antibody in most patients. Discrepant ELISA results, mostl y for elderly patients with duodenal ulcers, were attributed to cagA associ ated variation, particularly to the presence of mixed cagA+/cagA- cell vari ants in the infecting strain population. Tests for anti-CagA serum antibody were unreliable for predicting severity of clinical disease associated wit h H pylori infection in this series of patients.