Helicobacter pylori vac A genotype is a predominant determinant of immune response to Helicobacter pylori CagA

AIM To evaluate the frequency of Helicobacter pylori(H. pylori) Cag A antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori Cag A-immune response.METHODS 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-Cag A) was correlated with H. pylori isolates(cag A, EPIYA, vac A s/m genotype), histology(Sydney classification) and mucosal interleukin-8(IL-8) m RNA and protein expression. Selected H. pylori strains were assessed for H. pylori Cag A protein expression and IL-8 induction in co-cultivation model with AGS cells.RESULTS Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for Cag A. Majority of H. pylori isolates were cag A gene positive(93.9%) with following vac A polymorphisms: 42.4% vac A s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-Cag AIg G seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cag A m RNA expression. V a c A s a n d m p o l y m o r p h i s m s w e r e t h e m a j o r determinants for positive(vac A s1m1) or negative(vac A s2m2) anti-Cag A 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 Cag A translocation, which showed only partial correlation with Cag A seropositivity in patients, supporting vac A as major co-determinant of the immune response.CONCLUSION Serological immune response to H. pylori cag A + strain in H. pylori infected patients is strongly associated with vac A polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.

Different antibiotic susceptibility between antrum and corpus of the stomach,a possible reason for treatment failure of Helicobacter pylori infection

AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications.Antimicrobial susceptibility to amoxicillin,clarithromycin,tetracycline,metronidazole,levofloxacin and rifabutin was tested with the E-test method on IsoSensitest agar with 10 vol%defibrinated horse blood.In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus,DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H.pylori isolates.RESULTS:Primary,secondary and tertiary resistance to clarithromycin was 6.9%,53.8%and 83.3%,retrospectively.Metronidazole and levofloxacin resistance also increased according to the number of previous treatments(17.2%,69.2%,83.3%;13.8%,23.1%,33.3%).Tertiary resistance to rifabutin was detected in12.5%of patients.In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable.Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2%(10/66)of the patients.Two out of those ten patients were naive to any H.pylori antibiotic treatment.The remaining eight patients previously received at least one eradication therapy.DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H.pylori strain.CONCLUSION:Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure.Resistant H.pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H.pylori susceptibility testing.