vacA genotype is a predominant determinant of immune response to CagA.

AIM

To evaluate the frequency of () CagA antibodies in infected subjects and to identify potential histopathological and bacterial factors related to CagA-immune response.

METHODS

Systematic data to isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-, anti-CagA) was correlated with isolates (, EPIYA, genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected strains were assessed for CagA protein expression and IL-8 induction in co-cultivation model with AGS cells.

RESULTS

Thirty point three percent of microbiologically confirmed infected patients were seropositive for CagA. Majority of isolates were gene positive (93.9%) with following polymorphisms: 42.4% , 23.2% and 34.3% . Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and mRNA expression. and polymorphisms were the major determinants for positive ( s1m1) or negative ( s2m2) anti-CagA serological immune response, which also correlated with the inflammatory potential in AGS cells. co-cultivation of representative strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting as major co-determinant of the immune response.

CONCLUSION

Serological immune response to + strain in infected patients is strongly associated with polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.