CagA Positivity Research Articles

Helicobacter pylori genotypes influence serum pepsinogen C levels.

Infection from Helicobacter pylori significantly influences pepsinogen A (PGA) and C (PGC) levels in serum. Increased PGA and PGC serum levels are observed in H. pylori positive patients, while a significant decrease is observed after eradication. Little is known about the relative role of H. pylori cytotoxic strains in this phenomenon. The aim of our study was to assess the influence of cagA genotype on circulating levels of PGA and PGC. We studied 81 consecutive H. pylori positive patients, 64 H. pylori negative patients and 18 healthy controls. H. pylori was evaluated histologically in two antral and two body biopsies (Giemsa and/or Warthin Starry staining). Extracted DNA was then submitted for PCR amplification of both the urease A and cagA genes. A serum obtained from each patient before endoscopy was used for specific radioimmunoassay measurement of PGA and PGC. The urease A gene was found in all H. pylori positive patients, the cagA gene was detected in 55 H. pylori positive patients and in none of the H. pylori negative patients. PGA and PGC levels were significantly higher in H. pylori positive than in H. pylori negative patients. A significant association was found between cagA and raised serum PGC levels in patients with antral gastritis but not in patients with peptic ulcer. Serum PGA levels were not affected by cagA. Our results indicate that cagA positivity may influence the circulating PGC levels, probably because it causes a higher grade of mucosal inflammation.

Country-specific constancy by age in cagA+ proportion of Helicobacter pylori infections.

Helicobacter pylori strains may be either cagA+ or cagA-, and in logitudinal studies, infection with a cagA+ strain has been associated with increased risk for the development of atrophic gastritis and cancer of the distal stomach. We sought to determine the relative proportion of strains producing CagA in different geographic locales, and the extent to which CagA seroprevalence varied in countries with different gastric and esophageal cancer rates. Using an enzyme-linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China, Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were relatively constant across gender and age groups. Reported gastric but not esophageal cancer rates for the 8 studied populations were significantly associated with H. pylori seroprevalence. Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates.

Heterogeneous Helicobacter pylori isolates from members of a family with a history of peptic ulcer disease

BACKGROUND & AIMS: Duodenal ulcer formation in persons infected with Helicobacter pylori correlates with the expression of the cytotoxin- associated gene A (cagA) and the vacuolating cytotoxin (VacA). The aim of this study was to assess the occurrence of cagA and VacA variants among H. pylori isolates. METHODS: H. pylori was isolated from 8 members of one family with a history of peptic ulcer disease (PUD). Each strain was characterized by random amplified polymorphic DNA (RAPD) fingerprinting. cagA was detected by polymerase chain reaction (PCR), Southern blotting, and colony hybridization. Viable H. pylori was added to mammalian cells to assess their cytotoxin activity. RESULTS: The RAPD patterns of the 8 patients' strains were similar. Analysis of 10 single colonies from the primary culture plates showed that all but 1 subject harbored multiple H. pylori subtypes. The proportion of cagA-positive colonies on the primary culture plates ranged from 0% to 90% between the isolates from all patients. In addition, the different H. pylori subtypes showed no cytotoxin activity in mammalian cells. CONCLUSIONS: Genotypic comparison of H. pylori isolated from different patients requires analysis of multiple colonies selected from the primary culture plate. In addition, infection by cagA- positive H. pylori in the family members with PUD (subjects 2-8) is consistent with the observed association between cagA positivity and PUD. (Gastroenterology 1996 Sep;111(3):638-47)

Helicobacter pylori and atrophic gastritis: importance of the cagA status.

Infection with Helicobacter pylori is a major risk factor for the development of atrophic gastritis and gastric cancer. H. pylori strains can differ with respect to the presence of cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen. H. pylori strains possessing cagA have been associated with enhanced induction of acute gastric inflammation. We investigated the relationship between cagA status and the development of atrophic gastritis in a cohort of subjects infected with H. pylori. Gastrointestinal endoscopy with biopsy sampling was used to study the natural history of gastritis in 58 subjects infected with H. pylori. Biopsy specimens were obtained before and after a mean follow-up period of 11.5 years (range, 10-13 years). The cagA status of each individual was determined at the follow-up visit with the use of an enzyme-linked immunosorbent assay designed to detect the presence of serum immunoglobulin G directed against the CagA protein. Two-sided Fisher's exact tests, McNemar's tests, Student's t tests, and Wilcoxon sum rank tests were used to analyze the data. Twenty-four (41%) of the 58 evaluated subjects had serum antibodies against CagA (i.e., they were cagA positive), and 34 subjects were cagA negative. At the initial visit, moderate to severe atrophic gastritis was observed in eight (33%) of the cagA-positive subjects and in six (18%) of the cagA-negative subjects. At that time, positive cagA status and gastric atrophy were not significantly related (P = .22; Fisher's exact test; odds ratio [OR] 2.33; 95% confidence interval [CI] = 0.58-9.65). During follow-up, 16 (36%) of the 44 initially atrophy-negative subjects developed atrophic gastritis (eight [50%] of 16 cagA-positive subjects versus eight [29%] of 28 cagA-negative subjects; P = .20, Fisher's exact test; relative risk [RR] = 1.75; 95% CI = 0.82-3.76). In six of these 16 subjects (five cagA positive versus one cagA negative), atrophic gastritis was accompanied by the development of intestinal metaplasia (i.e., a change in the type of specialized cells present) (P = .02; Fisher's exact test; RR = 9.06; 95% CI = 1.16-71.0). One of the initially atrophy-negative, cagA-positive subjects developed early gastric cancer. Four (29%) of the 14 subjects initially diagnosed with atrophic gastritis showed regression of atrophy during follow-up (one cagA positive and three cagA negative). Therefore, at the end of follow-up, 15 (62%) of the 24 cagA-positive subjects had atrophic gastritis compared with 11 (32%) of the 34 cagA-negative subjects (P = .02; Fisher's exact test; OR = 3.48; 95% CI = 1.02-12.18). Infection with cagA-positive H. pylori strains is associated with an increased risk for the eventual development of atrophic gastritis and intestinal metaplasia.