title: CagA and VacA polymorphisms do not correlate with severity of histopathological lesions in Helicobacter pylori-infected Greek children.
abstract: The presence of various numbers of EPIYA tyrosine phosphorylation motifs in the CagA protein of Helicobacter pylori has been suggested to contribute to pathogenesis in adults. In this prospective study, we characterized H. pylori isolates from symptomatic children, with reference to the diversity of functional EPIYA motifs in the CagA protein and vacA isotypes, and assessed the potential correlation with the histopathological manifestations of the infection. We analyzed 105 H. pylori isolates from 98 children and determined the diversity of EPIYA motifs in CagA by amplification and sequencing of the 3' variable region of the cagA gene as well as vacA isotypes for the signal, middle, and intermediate regions. CagA phosphorylation and levels of secreted IL-8 were determined following in vitro infection of AGS gastric epithelial cells. Histopathological evaluation of H. pylori colonization, activity, and severity of the associated gastritis was performed according to the updated Sydney criteria. EPIYA A (GLKN[ST]EPIYAKVNKKK), EPIYA B (Q[V/A]ASPEPIY[A/T]QVAKKVNAKI), and EPIYA C (RS[V/A]SPEPIYATIDDLG) motifs were detected in the ABC (46.6%) and ABCC (17.1%) combinations. No isolates harboring more than two EPIYA C motifs in CagA were found. The presence of isogenic strains with variable numbers of CagA EPIYA C motifs within the same patient was detected in seven cases. Occurrence of increasing numbers of EPIYA C motifs correlated strongly with presence of a high-vacuolation (s1 or s2/i1/m1) phenotype and age. A weak positive correlation was observed between vacuolating vacA genotypes and presence of nodular gastritis. However, CagA- and VacA-dependent pathogenicities were not found to contribute to severity of histopathology manifestations in H. pylori-infected children.
authors.affiliation: Hellenic Pasteur Institute, Athens, Greece. sgouras@pasteur.gr
authors.forename: Dionyssios N
authors.initials: DN
authors.lastname: Sgouras
authors.forename: Effrosini G
authors.initials: EG
authors.lastname: Panayotopoulou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papadakos
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martinez-Gonzalez
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Roumbani
authors.forename: Joanna
authors.initials: J
authors.lastname: Panayiotou
authors.forename: Cathy
authors.initials: C
authors.lastname: vanVliet-Constantinidou
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Mentis
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Roma-Giannikou
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D005260:Female; D005756:Gastritis / Q000473:pathology; D006115:Greece; D016481:Helicobacter Infections / Q000382:microbiology* / Q000473:pathology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C074689:VacA protein, Helicobacter pylori; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori