Published online Jul 14, 2017. doi: 10.3748/wjg.v23.i26.4712
Peer-review started: January 22, 2017
First decision: March 16, 2017
Revised: April 5, 2017
Accepted: May 19, 2017
Article in press: May 19, 2017
Published online: July 14, 2017
Processing time: 173 Days and 7 Hours
To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response.
Systematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-H. pylori, anti-CagA) was correlated with H. pylori isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells.
Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive (vacA s1m1) or negative (vacA s2m2) anti-CagA serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response.
Serological immune response to H. pylori cagA+ strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.
Core tip:Helicobacter pylori (H. pylori) related diseases are commonly associated with cagA+ strains, although seropositivity against CagA varies among different studies. In this prospective study, we evaluated potential factors related to the H. pylori CagA-immune response. We show that anti-CagA-IgG seropositivity was strongly associated with histopathological and inflammatory factors. Most importantly, we identified H. pylori vacA polymorphism as one of the main determinants of immune response to CagA and inflammatory potential of H. pylori strains ex vivo and in vitro. Our data support the crucial role of bacterial factors that co-determine the complex interaction with H. pylori and define the immune and clinical phenotypes of the infection.