Clinical relevance of the
            <i>Helicobacter pylori</i>
            gene for blood-group antigen-binding adhesin

Gerhard, Markus; Lehn, Norbert; Neumayer, Nina; Borén, Thomas; Rad, Roland; Schepp, Wolfgang; Miehlke, Stephan; Classen, Meinhard; Prinz, Christian

doi:10.1073/pnas.96.22.12778

Cited by 550 publications

(512 citation statements)

References 42 publications

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“…The babA2 gene has been strongly associated with cagA and vacA s1 in some populations [12]. Prevalence of babA2 positive strains is very heterogeneous and can be as high as 92.3 % [7,13,22].…”

Section: Discussionmentioning

confidence: 99%

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Correlation of Helicobacter pylori Genotypes with Gastric Histopathology in the Central Region of a South-European Country

et al. 2014

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Background Outcome of Helicobacter pylori (H. pylori) infection results from interaction of multiple variables including host, environmental and bacterial-associated virulence factors. Aim This study aimed to investigate the correlation of cagA, cagE, vacA, iceA and babA2 genotypes with gastric histopathology and disease phenotype in the central region of a South-European country. Methods This prospective study involved 148 infected patients (110 female; mean age 43.5 ± 13.4 years) submitted to endoscopy with corpus and antrum biopsies. H. pylori was cultured and DNA extracted from the isolates. Genotypes were determined by PCR. Histopathological features were graded according to the updated Sydney system and OLGA/OLGIM classification. Only patients with single H. pylori genotypes and complete histopathological results were included.Results Antrum samples presented higher degrees of atrophy, intestinal metaplasia, chronic inflammation and neutrophil activity. Genotype distribution was as follows: cagA-31.8 %; cagE-45.9 %; vacA s1a-24.3 %; vacA s1b-19.6 %; vacA s1c-0.7 %; vacA s2-55.4 %; vacA m1-20.9 %; vacA m2-79.1 %; vacA s1m1-18.9 %; vacA s1m2-25.7 %; vacA s2m1-2 %; vacA s2m2-53.4 %; iceA1-33.8 %; iceA2-66.2 %; babA2-12.2 %. CagA genotype was significantly associated with higher degrees of intestinal metaplasia, neutrophil activity, chronic inflammation and OLGIM stages. BabA2 was linked with higher H. pylori density. Strains with vacA s1m1 or vacA s1m1 ? cagA positive genotypes had a significant association with peptic ulcer and vacA s2m2 with iron-deficient anemia. Conclusions cagA, vacA s1m1 and babA2 genotypes are relatively rare in the central region of Portugal. cagApositive strains are correlated with more severe histopathological modifications. This gene is commonly associated

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Section: Discussionmentioning

confidence: 99%

“…The blood group antigen binding adhesin (BabA), a protein encoded by the babA2 gene, binds to Lewis b antigens and ABO antigen [12]. There are three alleles for babA gene but only the babA2 gene product is functionally active.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Helicobacter pylori Genotypes with Gastric Histopathology in the Central Region of a South-European Country

et al. 2014

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“…The different primer sequences used in the present work have been described previously. 13 Sequences of the PCR products were confirmed by automated sequencing (ABI Prism 310 Genetic Analyser; Perkin Elmer, Branchburg, NJ, USA) using the same primer pairs.…”

Section: Detection Of H Pylori Genotypes and Sequencingmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

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Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway. Modern Pathology (2007) 20, 974-989;

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“…This suggests that H. pylori-associated disease is influenced not only by the pathogenic nature of the infecting strain but also by other factors. Genetic variability in host factors such as gender, 28,29 blood group antigens, 30 human lymphocyte antigen type, and the age of the host when the infection was acquired, may play a primary role in determining different clinical outcomes. 31 Environmental factors may also play a role in the outcome of the infection.…”

Section: Association Between H Pylori Infection and Diseasementioning

confidence: 99%

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Aguilar¹,

Ayala²,

Fierros-Zarate³

2001

Salud pública Méx

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Helicobacter pylori has acquired great importance during the last two decades, after being recognized as an important pathogen that infects a great portion of the human population. This microorganism is recognized as the main causal agent of chronic gastritis and duodenal ulcers, and it is associated with the subsequent development of gastric carcinoma. The pathogenic mechanisms of H. pylori and their relation to gastric ailments have not been clearly defined. However, at present it is well established that urease, vacuolating cytotoxin VacA, and the pathogenicity island (cag PAI) gene products, are the main factors of virulence of this organism. Thus, individuals infected with strains that express these virulence factors probably develop a severe local inflammation that may induce the development of peptic ulcer and gastric cancer. The way the infection spreads throughout the world suggests the possibility that there are multiple pathways of transmission. Due to the importance that H. pylori has acquired as a human pathogen, laboratories worldwide are attempting to develop a vaccine that confers long-term immunological protection against infection by this microorganism. Hence, the objective of this review is to present the most relevant findings of the biology of H. Pylori and its interaction with the human host. The full version of this paper is available too at: http:// www.insp.mx/salud/index.html ResumenHelicobacter pylori ha adquirido gran importancia durante las últimas dos décadas, al ser reconocido como un importante patógeno que infecta una gran porción de la población humana. Este microrganismo es reconocido como el principal agente que causa la gastritis crónica y la úlcera duodenal, además de que se ha asociado con el subsecuente desarrollo del carcinoma gástrico. Los mecanismos patogé-nicos de H. pylori y su relación con los padecimientos gás-tricos no se han definido en forma clara. Sin embargo, actualmente está bien establecido que la ureasa, la citotoxina vacuolizante VacA y los productos de los genes de la isla de patogenicidad (cag PAI) son los principales factores de virulencia de este organismo. Así, los individuos infectados con cepas que expresan dichos factores de virulencia, probablemente manifiesten una marcada inflamación local que podría inducir el desarrollo de úlcera péptica y cáncer gástri-co. La manera como la infección se propaga a nivel mundial sugiere la posibilidad de múltiples vías de transmisión. A consecuencia de la importancia que H. pylori ha adquirido como patógeno humano, los laboratorios del mundo se esfuerzan para desarrollar una vacuna que confiera protección inmunológica de larga duración contra la infección por este microorganismo. El objetivo de esta revisión es presentar los hallazgos más relevantes sobre la biología de H. pylori y su interacción con su huésped humano. El texto completo de este artículo también está disponible en:

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Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin

Cited by 550 publications

References 42 publications

Correlation of Helicobacter pylori Genotypes with Gastric Histopathology in the Central Region of a South-European Country

Correlation of Helicobacter pylori Genotypes with Gastric Histopathology in the Central Region of a South-European Country

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

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