Clinical presentation in relation to diversity within the Helicobacter pylori cag pathogenicity island.
OBJECTIVE
This study investigated the genetic diversity of the cag pathogenicity island (PAI) in Helicobacter pylori (H. pylori) in relation to clinical outcome and interleukin (IL)-8 production.


METHODS
Seven genes in the cag PAI (cagA, cagE, cagG, cagM, cagT, open reading frame 13 and 10) were examined by polymerase chain reaction and Southern blot hybridization using H. pylori from 120 patients with different presentations (duodenal ulcer, gastric cancer, gastritis alone). IL-8 production from AGS cells (gastric cancer cell line) cocultured with H. pylori was measured by ELISA.


RESULTS
An intact cag PAI was present in 104 (87%) isolates, and five (4%) had deletions within the cag PAI; 11 (9%) lacked the entire cag PAI. Clinical isolates containing the complete cag PAI induced a greater secretion of IL-8 as compared with those without the cag PAI (3048 +/- 263 vs 480 +/- 28 pg/ml, p < 0.001). Deletion of only cagG reduced IL-8 secretion by two thirds. Deletions of more than one locus reduced IL-8 secretion to background. A similar proportion of H. pylori from patients with gastritis, duodenal ulcer, or gastric cancer had intact cag PAI (88%, 88%, and 85%, respectively). Although the presence of cagG was a better predictor of the presence of an intact cag PAI than cagA or cagE, the presence or absence of any of these genes had no association with clinical presentation.


CONCLUSIONS
Although the cag PAI plays an important role in IL-8 production, clinical presentation cannot be predicted by the presence of an intact cag PAI or any of these seven cag PAI genes.
D000328:Adult; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics; D004381:Duodenal Ulcer / Q000235:genetics* / Q000382:microbiology*; D005260:Female; D005756:Gastritis / Q000235:genetics* / Q000382:microbiology*; D014644:Genetic Variation / Q000235:genetics*; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C103937:PicB protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori