Reliability of Helicobacter pylori and CagA serological assays

Background serological assays for Helicobacter pylori are commonly used without knowledge of reliability. This information is needed to define the ability of serological tests to determine either new cases of infection or loss of infection in longitudinal studies. We evaluated the reproducibility and the interrelationships of serological test results for H. pylori and cytotoxin-associated gene product A (CagA) enzyme-linked immunoassays within a subset of participants in a population-based study. Stored samples from 1,229 participants in the third U.S. National Health and Nutrition Examination Survey were replicate serologically tested for H. pylori and CagA. Overall disagreement was 3.4% between duplicate tests for H. pylori (or 2.3% if equivocal results were disregarded). Six percent of samples positive on the first test had an immune serum ratio at least 30% lower on repeat testing. The odds ratio for H. pylori seropositivity on retesting was 2.8 (95% confidence interval [CI] = 1.8 to 4.5) when CagA serology was positive versus when it was negative. CagA antibody was found among 47.8% of H. pylori-equivocal and 7.0% of H. pylori-negative samples. CagA-positive yet H. pylori-negative samples were more likely to occur among Mexican Americans (odds ratio, 5.2; 95% CI = 2.4 to 11.4) and non-Hispanic blacks (odds ratio, 5.5; 95% CI = 2.3 to 13.0) than among non-Hispanic whites. Relying on repeated H. pylori serological tests over time to determine infection rates may result in misinterpretation due to limits in test reproducibility. CagA testing may have a role in verifying infection.