Presence of Thrombin-Activatable Fibrinolysis Inhibitor in Helicobacter pylori-Associated Gastroduodenal Disease

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the regulation of coagulation and inflammation. In addition to inhibiting the fibrinolytic system, TAFI may also regulate the bradykinin and complement systems. We hypothesized that TAFI also plays a role in defense mechanisms of the gastric mucosa during Helicobacter pylori infection. This study comprised 65 patients with gastroduodenal disorders: 41 patients with H. pylori infection, 13 without, and 11 patients with cured H. pylori infection. The gastric intramucosal concentrations of TAFI were measured by enzyme immunoassay. The gastric levels of TAFI and plasminogen activator inhibitor-1 were significantly increased in patients with H. pylori compared to those without infection or cured H. pylori . The presence of TAFI was detected in gastric mucosal epithelial cells. The concentration of TAFI was correlated with the degree of gastric mucosal atrophy, inflammation, and disease activity. These results show that TAFI is present in the gastric mucosa and that it may play a role in the pathogenesis of H. pylori infection-associated gastroduodenal disorders.     

Association between cagA and vacA genotypes and pathogenesis in a Helicobacter pylori infected population from South-eastern Sweden

ABSTRACT: BACKGROUND: Chronic gastritis, peptic ulcer disease, and gastric cancer have been shown to be related toinfection with Helicobacter pylori (H. pylori). Two major virulence factors of H. pylori,CagA and VacA, have been associated with these sequelae of the infection. In this study, totalDNA was isolated from gastric biopsy specimens to assess the cagA and vacA genotypes. RESULTS: Variations in H. pylori cagA EPIYA motifs and the mosaic structure of vacA s/m/i/dayregions were analysed in 155 H. pylori-positive gastric biopsies from 71 individuals usingPCR and sequencing. Analysis of a possible association between cagA and vacA genotypesand gastroduodenal pathogenesis was made by logistic regression analysis. We found that H. pylori strains with variation in the number of cagA EPIYA motif variants present in the samebiopsy correlated with peptic ulcer, while occurrence of two or more EPIYA-C motifs wasassociated with atrophy in the gastric mucosa. No statistically significant relation betweenvacA genotypes and gastroduodenal pathogenesis was observed. CONCLUSIONS: The results of this study indicate that cagA genotypes may be important determinants in thedevelopment of gastroduodenal sequelae of H. pylori infection. In contrast to other studies,vacA genotypes were not related to disease progression or outcome. In order to fullyunderstand the relations between cagA, vacA and gastroduodenal pathogenesis, themechanisms by which CagA and VacA act and interact need to be further investigated.     

The Correlation in Dyspeptic Patients of Helicobacter Pylori Infection with Changes in lnterdigestive Gastroduodenal Motility Patterns but not in Gastric Emptying

Background Available data conflict regarding the possible relation between chronic gastritis, Helicohacter pylori (H p), and gastric motor disorders in nonulcer dyspepsia. The aim of this study, therefore, was (1) evaluate both gastroduodenal fasting motility and gastric emptying in subjects with functional dyspepsia, with and without gastritis, and (2) to correlate the motility pattern to H p infection.
Materials and Methods. Thirty-eight patients were studied, 20 positive for Hp infection (15 with gastritis) and 18 Hp-negative (8 with gastritis). All the subjects underwent 240-minute manometric recording of the interdigestive migrating motor complex, with evaluation of gastric and duodenal motility pattern and scintigraphic study of gastric emptying.
Results. Whereas gastric emptying half-times did not differ in the subgroups of dyspeptic patients, a significant reduction of gastric phase 111s of the migrating motor complex was detected between Hp-positive and Hp negative subjects, both in overall patients (p < .01) and in patients with gastritis (p < .05).
Conclusions. Hp infection seems to be related to a reduction of interdigestive gastric activity fronts, though it does not affect gastric emptying. The conflicting data regarding gastric emptying and interdigestive motility in Hp infection could be explained as probably investigating two different functional aspects.     

幽门螺杆菌感染对胃酸及胃液氨浓度的影响

目的 :探讨幽门螺杆菌 (Hp)感染对胃酸分泌及氨浓度的影响以及十二指肠 (DU)的关系。方法 :对DU患者 ,Hp根治前后的胃液pH ,空腹胃酸及氨浓度之间的关系进行研究。结果 :Hp阳性的UC患者其空腹胃酸、氨浓度显著高于正常对照组 (P <0 0 5 ) ,而根除Hp后 ,空腹胃酸显著下降 ,接近正常水平 (P >0 0 5 ) ,氨浓度明显下降。结论 :Hp感染使DU患者胃酸分泌增多 ,二者之间的相互作用在DU的发病中占有重要地位。     

Crohn disease ATG16L1 polymorphism increases susceptibility to infection with Helicobacter pylori in humans

Autophagy plays key roles both in host defense against bacterial infection and in tumor biology. Helicobacter pylori (H. pylori) infection causes chronic gastritis and is the single most important risk factor for the development of gastric cancer in humans. Its vacuolating cytotoxin (VacA) promotes gastric colonization and is associated with more severe disease. Acute exposure to VacA initially triggers host autophagy to mitigate the effects of the toxin in epithelial cells. Recently, we demonstrated that chronic exposure to VacA leads to the formation of defective autophagosomes that lack CTSD/cathepsin D and have reduced catalytic activity. Disrupted autophagy results in accumulation of reactive oxygen species and SQSTM1/p62 both in vitro and in vivo in biopsy samples from patients infected with VacA (+) but not VacA (-) strains. We also determined that the Crohn disease susceptibility polymorphism in the essential autophagy gene ATG16L1 increases susceptibility to H. pylori infection. Furthermore, peripheral blood monocytes from individuals with the ATG16L1 risk variant show impaired autophagic responses to VacA exposure. This is the first study to identify both a host autophagy susceptibility gene for H. pylori infection and to define the mechanism by which the autophagy pathway is affected following H. pylori infection. Collectively, these findings highlight the synergistic effects of host and bacterial autophagy factors on H. pylori pathogenesis and the potential for subsequent cancer susceptibility.     

Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin

Helicobacter pylori infection is associated with gastritis, ulcerations, and gastric adenocarcinoma. H. pylori secretes the vacuolating cytotoxin (VacA), a major pathogenicity factor. VacA has immunosuppressive effects, inhibiting interleukin-2 (IL-2) secretion by interference with the T cell receptor/IL-2 signaling pathway at the level of calcineurin, the Ca2+-calmodulin-dependent phosphatase. Here, we show that VacA efficiently enters activated, migrating primary human T lymphocytes by binding to the beta2 (CD18) integrin receptor subunit and exploiting the recycling of lymphocyte function-associated antigen (LFA)-1. LFA-1-deficient Jurkat T cells were resistant to vacuolation and IL-2 modulation, and genetic complementation restored sensitivity to VacA. VacA targeted human, but not murine, CD18 for cell entry, consistent with the species-specific adaptation of H. pylori. Furthermore, expression of human integrin receptors (LFA-1 or Mac-1) in murine T cells resulted in VacA-mediated cellular vacuolation. Thus, H. pylori co-opts CD18 as a VacA receptor on human T lymphocytes to subvert the host immune response.     

Helicobacter pylori vacuolating cytotoxin, VacA, is responsible for gastric ulceration

Pathogenic strains of Helicobacter pylori produce a potent exotoxin, VacA, which causes progressive vacuolation as well as gastric injury. Most H. pylori strains secrete VacA into the extracellular space. After exposure of VacA to acidic or basic pH, re-oligomerized VacA (mainly 6 monomeric units) at neutral pH is more toxic. Although the mechanisms have not been defined, VacA induces multiple effects on epithelial and lymphatic cells, i.e., vacuolation with alterations of endo-lysosomal function, anion-selective channel formation, mitochondrial damage, and the inhibition of primary human CD4+ cell proliferation. VacA binds to two types of receptor-like protein tyrosine phosphatases (RPTP), RPTPalpha and RPTPbeta, on the surface of target cells. Oral administration of VacA to wild-type mice, but not to RPTPbeta KO mice, results in gastric ulcers, suggesting that RPTPbeta is essential for intoxication of gastric tissue by VacA. As the potential roles of VacA as a ligand for RPTPalpha and RPTPbeta are only poor understood, further studies are needed to determine the importance of VacA in the pathogenisis of disease due to H. pylori infection.     

CagA and VacA are immunoblot markers of past Helicobacter pylori infection in atrophic body gastritis

BACKGROUND AND AIM: Atrophic body gastritis (ABG) may be induced by H. pylori infection. It is difficult to diagnose H. pylori infection in this condition, since during progression of body atrophy the bacterium disappears. In 30% of patients with ABG no sign of H. pylori infection is detectable. We aimed to investigate whether patients with ABG, classified as H. pylori-negative by conventional methods (ELISA serology and Giemsa stain histology), have been previously exposed to the infection. METHODS: Case series consisted of 138 outpatients with ABG, of whom 31 are H. pylori negative (histology and ELISA serology), and 107 are H. pylori related (histology and ELISA serology positive: active infection, n = 29; only serology positive: past infection, n = 78). Thirty control subjects who were H. pylori negative at histology and ELISA serology were investigated. Immunoblotting of sera against H. pylori whole-cell protein lysate was performed. RESULTS: None of the control sera recognized CagA, VacA, heat-shock protein B, and urease B, yielding a specificity of 100%. All H. pylori-negative patients with ABG showed immunoblotting seroreactivity, including in each case either CagA or VacA. The concomitant seroreactivity against CagA and VacA was highly prevalent in the H. pylori-negative patients with ABG, comparable to those with active infection (77.4% vs. 86.2%) and with past infection (vs. 61.5%). CONCLUSIONS: Immunoblotting against CagA and VacA is able to prove past exposure to H. pylori infection in all patients with ABG defined as H. pylori-negative by conventional methods, suggesting a hidden role of H. pylori infection in gastric atrophy also in these patients.     

Effect of H. pylori infection on the expression of cyclooxygenase-2 in human gastric mucosa

Cyclooxygenase-1 is the primary isoform responsible for the production of cytoprotective prostaglandins (PGE(2) and PGI(2)) in the stomach. In contrast COX-2 is induced at the sites of inflammation. Using Helicobacter pylori infection as a model of inflammation, this study was designed to evaluate the effects of H. pylori infection on prostanoid synthesis and expression of COX-2 in human gastric mucosa.Prostaglandin (PGE(2)) and prostacyclin (PGI(2)) synthesis in gastric biopsies obtained from 21 patients undergoing diagnostic endoscopy, were determined. H. pylori was detected by CLO test, histology and culture. Biopsy samples were incubated either with NS-398, selective COX-2 inhibitor or aspirin. Samples were also treated with endotoxin (LPS) in order to induce COX-2 expression. Tissue was also analysed for COX-2 expression in vivo by immunohistochemistry.In 15 out of 21 patients, H. pylori was detected by at least two of the three methods. Higher levels of PGE(2) and PGI(2) were seen in patients infected with H. pylori (191+/-30 and 245+/-88ng/mg protein, respectively) compared with non-infected patients (77+/-17 and 120+/-36ng/mg protein, respectively). There was significant inhibition of PGE(2) and PGI(2) with aspirin in both H. pylori infected (28+/-6.6 and 53+/-43ng/mg, respectively) and in non-infected patients (16+/-7 and 12.5+/-3.5ng/mg protein, respectively). However, NS-398 and LPS did not alter prostaglandin function significantly. Immunohistochemistry in all patients irrespective of Hp status demonstrated expression of COX-2.Lower concentration of constitutive expression of COX-2 was detected in human gastric mucosa by immunohistochemistry, however, H. pylori infection failed to induce COX-2 protein. In addition, increased prostaglandin synthesis in Hp-infected patients appears to be COX-1 mediated rather than COX-2. Furthermore, failure of endotoxaemia-treated sample to produce more PGE(2) in the face of enhanced COX-2 expression in gastric mucosa further suggests that increased prostanoids in human gastric stomach are COX-1 mediated.     

幽门螺杆菌在慢性阻塞性肺疾病发生及 发展过程中的作用

目的研究幽门螺杆菌(Helicobacter pylori,H.pylori)在慢性阻塞性肺疾病(COPD)发生及发展过程中的作用。方法对85例COPD患者(COPD组)和85例体检健康者(对照组)进行血清抗H.pylori抗体(抗Hp-IgG)检测,比较两组的抗Hp-IgG水平及H.pylori阳性率。全部COPD患者均行肺功能和免疫功能检查,分析抗Hp-IgG水平与COPD严重程度的相关性,比较合并H.pylori感染与无H.pylori感染COPD患者之间,以及合并H.pylori感染COPD患者根除H.pylori前后免疫功能的差异。结果 COPD组血清抗Hp-IgG水平和H.pylori阳性率均明显高于对照组(P0.05),FEV1%预计值与血清抗Hp-IgG水平呈负相关(P0.05)。与无H.pylori感染的COPD患者相比,合并H.pylori感染的COPD患者外周血CD_3~+和CD_4~+T细胞含量、CD_4~+/CD_8~+比值、血清免疫球蛋白(IgA、IgG、IgM)水平均明显较低(P0.05),经H.pylori根除治疗后各指标水平明显升高(P0.05)。结论 H.pylori感染可导致宿主免疫功能紊乱,可能因此促进了COPD的发生和发展。根除H.pylori可明显改善合并H.pylori感染COPD患者的免疫功能,有利于患者恢复。     

Prevalence of CagA, VacA Antibodies in Symptomatic and Asymptomatic Children with Helicobacter pylori Infection

Background. Limited data are available on the prevalence of CagA and VacA Helicobacter pylori antibodies in children. The aim of this study was to investigate the antibody prevalence to the H. pylori virulence factors CagA and VacA in symptomatic and asymptomatic children with H. pylori infection and to correlate these antibodies with the severity of gastric inflammation or density of H. pylori organisms in the gastric mucosa.
Materials and Methods. Twenty-three symptomatic children and 132 asymptomatic children with positive H. pylori serology participated in this study. Anti– H. pylori IgG antibody and CagA or VacA H. pylori antibodies were measured by enzyme immunoassay (HM-CAP; sensitivity and specificity> 90%) and Western immunoblot (Helicoblot 2.0) methods, respectively. Gastric inflammation and H. pylori density were graded histologically using the revised Sydney criteria.
Results. The prevalence of CagA and VacA antibodies were 69% and 35% in symptomatic children and 54% and 52% in asymptomatic children, respectively. Multiple regression analysis showed a correlation between CagA antibody and the severity of gastritis but no correlation with other histological features, including the number of neutrophils or lymphoid follicles. Neither antibody correlated with the degree of bacterial density in the gastric mucosa.
Conclusion. CagA and VacA H. pylori antibodies are common in the pediatric population. The combined CagA/VacA antibodies correlated weakly with the degree of mucosal inflammation.     

CagA and VacA: Virulence Factors of Helicobacter pylori in Thai patients with Gastroduodenal Diseases

Background. The aim of this study was to assess the seroprevalence of cytotoxin-associated gene A ( cag A) and vacuolating cytotoxin gene A ( vac A) of Helicobacter pylori in selected Thai populations with specific gastroduodenal diseases.
Materials and Methods. The immunoblot assay was used to detect serum antibodies against CagA and VacA obtained from the following patients: 87 cases of nonulcer dyspepsia (NUD), 61 cases of duodenal ulcer (DU), 49 cases of gastric ulcer (GU), and 10 cases of gastric cancer (GC).
Results. Serum antibodies to CagA were detected in 75.4% of all patients (70.1% of NUD, 78.7% of DU, 77.6% of GU, and 90% of GC). Although the prevalence of CagA seropositivity in GC patients was higher than in the other three groups, the difference was not statistically significant ( p > .05).
Conclusions. The high seroprevalence of the CagA-positive H. pylori strain in patients with peptic ulcer, GC, and NUD indicates that this strain is common in Thai patients with gastroduodenal diseases. Furthermore, phenotypic classification of H. pylori into type 1 (CagA-positive, VacA-positive) and type 2 (CagA-negative, VacA-negative) is not a useful marker for screening patients with severe forms of gastroduodenal diseases.     

The Helicobacter pylori VacA cytotoxin activates RBL-2H3 cells by inducing cytosolic calcium oscillations

Helicobacter pylori causes an acute inflammatory response followed by chronic infection of the human gastric mucosa. Identification of the bacterial molecules endowed with a pro-inflammatory activity is essential to a molecular understanding of the pathogenesis of H. pylori associated diseases. The vacuolating cytotoxin A (VacA) induces mast cells to release pro-inflammatory cytokines. Here, we show that VacA activates the mast cell line RBL-2H3 by rapidly inducing an oscillation of the level of cytosolic calcium with exocytosis of secretory granules. Cytosolic calcium derives mainly from intracellular stores. VacA also stimulates a calcium-dependent production of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha). These observations indicate that VacA may act as a pro-inflammatory factor of H. pylori at very early stages of the innate immune response.     

The role of CagA status in gastric and extragastric complications of Helicobacter pylori.

Two major markers of virulence have been described in H. pylori. The first is a secreted protein (VacA) that is toxic to human cells in tissue culture. This cytotoxin causes vacuolation of epithelial cells in vitro and induces epithelial cell damage in mice. The second is a 40-Kb pathogenicity island for which the gene cagA (cytotoxin-associated gene A) is a marker. Approximately 60% of H. pylori isolates in Western countries are cagA+. The protein encoded by cagA+ has a molecular weight of 120-140 kDa and exhibits sequence heterogeneity among strains isolated from Western and Eastern countries. Although no specific function has been identified for CagA, there is increasing evidence that cagA+ strains are associated with increased intensity of gastric inflammation and increased mucosal concentration of particular cytokines including interleukin 8. Inactivation of picB (Hp 0544) or any of several other genes in the cag island ablates the enhanced IL-8 secretion of human gastric epithelial cells in tissue culture. Furthermore, persons colonized with cagA+ strains have an increased risk of developing more severe gastric diseases such as peptic ulcer and distal (non-cardia) gastric cancer than those harboring cagA- strains. We investigated the role of cagA status in both gastroduodenal and extragastroduodenal disease with H. pylori. Among the diseases limited to the antrum and body of the stomach and the duodenum, we demonstrated a correlation between CagA seropositivity and peptic ulcer disease. We also showed correlation between distal gastric cancer rated and CagA prevalence in populations in both developed and developing countries. In addition, we found that for several Asian populations, the relationship between CagA seropositivity and gastroduodenal diseases was complex. For extragastroduodenal diseases, our results confirmed previous reports that demonstrated that CagA status did not play a role in diseases such as rheumatoid arthritis and hyperemesis gravidarum. However, we found a clear negative association between the presence of a positive response to CagA and esophageal diseases. Therefore, CagA seropositivity (and thus gastric carriage) is associated with increased risks of certain diseases (involving the lower stomach and duodenum) and decreased risks of GERD and its sequelae. This apparent paradox can best be explained by differences in the interaction of cagA+ and cagA- strains with their hosts.     

cag+ Helicobacter pylori induce transactivation of the epidermal growth factor receptor in AGS gastric epithelial cells

The gastric pathogen Helicobacter pylori is known to activate epithelial cell signaling pathways that regulate numerous inflammatory response genes. The aim of this study was to elucidate the pathway leading to extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in H. pylori-infected AGS gastric epithelial cells. We find that H. pylori, via activation of the epidermal growth factor (EGF) receptor activates the small GTP-binding protein Ras, which in turn, mediates ERK1/2 phosphorylation. cag+ strains of H. pylori are able to induce greater EGF receptor activation than cag- strains, and studies with isogenic mutants indicate that an intact type IV bacterial secretion system is required for this effect. Blockade of EGF receptor activation using tyrphostin AG1478 prevents H. pylori-mediated Ras activation, inhibits ERK1/2 phosphorylation, and substantially decreases interleukin-8 gene expression and protein production. Investigations into the mechanism of EGF receptor activation, using heparin, a metalloproteinase inhibitor and neutralizing antibodies reveal that H. pylori transactivates the EGF receptor via activation of the endogenous ligand heparin-binding EGF-like growth factor. Transactivation of gastric epithelial cell EGF receptors may be instrumental in regulating both proliferative and inflammatory responses induced by cag+ H. pylori infection.     

Human polymorphonuclear leukocytes are sensitive in vitro to Helicobacter pylori vaca toxin

BACKGROUND: Interactions between bacterial components and polymorphonuclear leukocytes (PMNL) play a major pathogenic role in Helicobacter pylori-associated diseases. Activation of PMNL can be induced by contact with whole bacteria or by different H. pylori products released in the extracellular space either by active secretion or by bacterial autolysis. Among these products, H. pylori VacA is a secreted toxin inducing vacuolation and apoptosis of epithelial cells. METHODS AND RESULTS: We found that non-opsonic human PMNL were sensitive to the vacuolating effect of VacA+ broth culture filtrate (BCF) and of purified VacA toxin. PMNL incubated with VacA+ BCF showed Rab7-positive large intracytoplasmic vacuoles. PMNL preincubation with H. pylori BCF of different phenotypes dramatically potentialized the oxidative burst induced by zymosan, increased phagocytosis of opsonized fluorescent beads, and up-regulated CD11b cell surface expression, but independently of the BCF VacA phenotype. Moreover, by using purified VacA toxin we showed that vacuolation induced in PMNL did not modify the rate of spontaneous PMNL apoptosis measured by caspase 3 activity. CONCLUSIONS: Taken together, these data showed that human PMNL is a sensitive cell population to H. pylori VacA toxin. However, activation of PMNL (i.e., oxidative burst, phagocytosis, CD11b up-regulation) and PMNL apoptosis are not affected by VacA, raising question about the role of VacA toxin on PMNL in vivo.     

Helicobacter pylori, T cells and cytokines: the "dangerous liaisons"

Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop chronic and life threatening diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune gastritis. The type of host immune response against H. pylori is crucial for the outcome of the infection. A predominant H. pylori-specific Th1 response, characterized by high IFN-gamma, TNF-alpha, and IL-12 production associates with peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit abnormal help for autologous B-cell proliferation and reduced perforin- and Fas-Fas ligand-mediated killing of B cells. In H. pylori-infected patients with autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross-recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen. These data suggest that peptic ulcer can be regarded as a Th1-driven immunopathological response to some H. pylori antigens, whereas deregulated and exhaustive H. pylori-induced T cell-dependent B-cell activation can support the onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead in some individuals to gastric autoimmunity via molecular mimicry.     

Importance of EGF receptor, HER2/Neu and Erk1/2 kinase signalling for host cell elongation and scattering induced by the Helicobacter pylori CagA protein: antagonistic effects of the vacuolating cytotoxin VacA

Helicobacter pylori is the causative agent of gastric pathologies ranging from chronic gastritis to peptic ulcers and even cancer. Virulent strains carrying both the cag pathogenicity island ( cag PAI) and the vacuolating cytotoxin VacA are key players in disease development. The ca gPAI encodes a type IV secretion system (T4SS) which forms a pilus for injection of the CagA protein into gastric epithelial cells. Injected CagA undergoes tyrosine phosphorylation and induces actin-cytoskeletal rearrangements involved in host cell scattering and elongation. We show here that the CagA-induced responses can be inhibited in strains expressing highly active VacA. Further investigations revealed that VacA does not interfere with known activities of phosphorylated CagA such as inactivation of Src kinase and cortactin dephosphorylation. Instead, we demonstrate that VacA exhibits inactivating activities on the epidermal growth factor receptor EGFR and HER2/Neu, and subsequently Erk1/2 MAP kinase which are important for cell scattering and elongation. Inactivation of vacA gene, downregulation of the VacA receptor RPTP-α, addition of EGF or expression of constitutive-active MEK1 kinase restored the capability of H. pylori to induce the latter phenotypes. These data demonstrate that VacA can downregulate CagA's effects on epithelial cells, a novel molecular mechanism showing how H. pylori can avoid excessive cellular damage.     

Combined serum IgG response to Helicobacter pylori VacA and CagA predicts gastric cancer

Helicobacter pylori is a major factor for the development of gastric cancer. The aim of this study was to define serum antibody patterns associated with H. pylori infection in patients with gastric cancer using a Western blot technique. Serum samples collected from 115 patients with gastric cancer and 110 age- and gender-matched patients without gastrointestinal diseases were tested for IgG antibodies to H. pylori antigens (outer membrane proteins and whole cell preparations). No significant differences were found between patients with and without gastric cancer using outer membrane proteins (82% and 73%, P>0.05) or whole cell antigens (84% and 76%, P>0.05), respectively. The significant differences between patients with and without gastric cancer were associated with bands of 94 kDa (54% and 20%, P<0.001) and 30 kDa (65% and 44%, P<0.01). A combination of antibodies to 85 kDa (VacA) and 120 kDa (CagA) was significantly (P<0.01) more frequent in gastric cancer patients than in patients without gastric cancer. The detection of antibodies to 94- and 30-kDa bands, in association with the determination of serum antibodies to CagA+/VacA+, may have a prospective value in assessment of the risk of developing of gastric cancer.     

Potential role of CagA in the inhibition of T cell reactivity in Helicobacter pylori infections

The pathogenicity of chronic gastroduodenal diseases is very often related to Helicobacter pylori infections. Most H. pylori strains carry the cagA gene encoding an immunodominant 120- to 128-kDa protein which is considered a virulence marker. The majority of CagA-positive H. pylori isolates also produce a 95-kDa protein cytotoxin (VacA) causing vacuolation and degradation of mammalian cells. In our previous study we have shown that live H. pylori bacteria and their sonicates inhibit PHA-driven proliferation of human T lymphocytes. The H. pylori CagA and VacA proteins were suspected of a paralyzing effect of H. pylori on T cell proliferation. In this report, by using isogenic H. pylori mutant strains defective in CagA and VacA proteins, we determined that CagA is responsible for the inhibition of PHA-induced proliferation of T cells.