Performance of a one-step fecal sample-based test for diagnosis of Helicobacter pylori infection in primary care and mass screening settings.

BACKGROUND/PURPOSE: An alternative screening test is needed to efficiently eradicate Helicobacter pylori from a population with prevalent upper gastrointestinal lesions. We evaluated the performance of a new one-step fecal test for H. pylori for diagnosis of H. pylori infection in Taiwan. METHODS: We developed a fecal test to detect H. pylori based on the immunochronomatographic assay and a mixture of monoclonal antibodies. We first recruited symptomatic patients from the primary care setting to evaluate fecal test performance using a reference standard consisting of (13)C urea breath test, rapid urease test, and histology. We also compared the performance of the fecal test with that of others. Next, we recruited asymptomatic participants from the mass screening setting to evaluate population attendance for the fecal test and compared its performance with that of (13)C urea breath test. RESULTS: In the primary care setting, 117 patients were recruited; H. pylori infection was confirmed in 58 (49.6%). Fecal test sensitivity, specificity, positive and negative predictive values, and accuracy were 88.0% [95% confidence interval (CI): 79.6-96.4%], 100%, 100%, 89.4% (95% CI, 82.0-96.8%), and 94% (95% CI, 89.7-98.3%), respectively. Fecal test specificity and positive predictive value were significantly higher than those of the serological test, whereas the sensitivity and negative predictive value were lower than those of the (13)C urea breath test (p < 0.05). In the mass screening setting, 2720 of 3520 invited individuals participated (77.3%; 95% CI, 76-78.7%); 649 (23.9%) showed positive results. Concordance rate and kappa statistic between the fecal test and (13)C urea breath test were 91.7% (563/614; 95% CI, 89.9-94.1%) and 0.78 (95% CI, 0.73-0.84), respectively. CONCLUSION: Given the acceptable sensitivity, excellent specificity, and high participation rate to screening, the one-step H. pylori stool antigen test is feasible for wide application in the community.

Low-dose antigen promotes induction of FOXP3 in human CD4+ T cells.

Low Ag dose promotes induction and persistence of regulatory T cells (Tregs) in mice, yet few studies have addressed the role of Ag dose in the induction of adaptive CD4(+)FOXP3(+) Tregs in humans. To this end, we examined the level of FOXP3 expression in human CD4(+)CD25(-) T cells upon activation with autologous APCs and varying doses of peptide. Ag-specific T cells expressing FOXP3 were identified by flow cytometry using MHC class II tetramer (Tmr). We found an inverse relationship between Ag dose and the frequency of FOXP3(+) cells for both foreign Ag-specific and self Ag-specific T cells. Through studies of FOXP3 locus demethylation and helios expression, we determined that variation in the frequency of Tmr(+)FOXP3(+) T cells was not due to expansion of natural Tregs, but instead, we found that induction, proliferation, and persistence of FOXP3(+) cells was similar in high- and low-dose cultures, whereas proliferation of FOXP3(-) T cells was favored in high Ag dose cultures. The frequency of FOXP3(+) cells positively correlated with suppressive function, indicative of adaptive Treg generation. The frequency of FOXP3(+) cells was maintained with IL-2, but not upon restimulation with Ag. Together, these data suggest that low Ag dose favors the transient generation of human Ag-specific adaptive Tregs over the proliferation of Ag-specific FOXP3(-) effector T cells. These adaptive Tregs could function to reduce ongoing inflammatory responses and promote low-dose tolerance in humans, especially when Ag exposure and tolerance is transient.