lewis-x-antigen and Helicobacter-Infections

Helicobacter pylori adhesion to gastric epithelial cells constitutes a key step in the establishment of a successful infection of the gastric mucosa. The high representation of outer membrane proteins in the bacterial genome suggests the relevance of those proteins in the establishment of profitable interactions with the host gastric cells. Gastric epithelial cells are protected by a mucous layer gel, mainly consisting of the MUC5AC and MUC6 mucins. In addition to this protective role, mucins harbor glycan-rich domains that constitute preferential binding sites of many pathogens. In this article we review the main players in the process of H. pylori adhesion to gastric epithelial cells, which contribute decisively to the high prevalence and chronicity of H. pylori infection. The BabA adhesin recognizes both H-type 1 and Lewis b blood-group antigens expressed on normal gastric mucosa of secretor individuals, contributing to the initial steps of infection. Upon colonization, persistent infection induces an inflammatory response with concomitant expression of sialylated antigens. The SabA adhesin mediates H. pylori binding to inflamed gastric mucosa by recognizing sialyl-Lewis a and sialyl-Lewis x antigens. The expression of the BabA and SabA adhesins is tightly regulated, permitting the bacteria to rapidly adapt to the changes of glycosylation of the host gastric mucosa that occur during infection, as well as to escape from the inflammatory response. The growing knowledge of the interactions between the bacterial adhesins and the host receptors will contribute to the design of alternative strategies for eradication of the infection.

Topics: Adhesins, Bacterial; Animals; Antigens, Bacterial; Bacterial Adhesion; Epithelial Cells; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen

Helicobacter pylori is a Gram-negative bacterium that infects over 50% of the world's population. This organism causes various gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer. H. pylori possesses lipopolysaccharides that share structural similarity to Lewis blood group antigens in gastric mucosa. Such antigenic mimicry could result in immune tolerance against antigens of this pathogen. On the other hand, H. pylori colonizes gastric mucosa by utilizing adhesins that bind Lewis blood group antigen-related carbohydrates expressed on gastric epithelial cells. After colonization, H. pylori induces acute inflammatory responses mainly by neutrophils. This acute phase is gradually replaced by a chronic inflammatory response. In chronic gastritis, lymphocytes infiltrate the lamina propria, and such infiltration is facilitated by the interaction between L-selectin on lymphocytes and peripheral lymph node addressin (PNAd), which contains 6-sulfo sialyl Lewis X-capped O-glycans, on high endothelial venule (HEV)-like vessels. H. pylori barely colonizes gland mucous cell-derived mucin where alpha1,4-GlcNAc-capped O-glycans exist. In vitro experiments show that alpha1,4-GlcNAc-capped O-glycans function as a natural antibiotic to inhibit H. pylori growth. These findings show that distinct sets of carbohydrates expressed in the stomach are closely associated with pathogenesis and prevention of H. pylori-related diseases, providing therapeutic potentialities based on specific carbohydrate modulation.

Topics: Adhesins, Bacterial; Animals; Chronic Disease; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; L-Selectin; Lewis X Antigen; Lipopolysaccharides; Molecular Mimicry; Mucin-2; Neutrophils; O Antigens; Oligosaccharides; Peptic Ulcer; Polysaccharides; Sialyl Lewis X Antigen; Stomach Neoplasms

Lymphocyte homing is mediated by a cascade of adhesive interactions between circulating lymphocytes and specialized endothelial cells comprising high endothelial venules (HEVs). Sulfated O-glycans expressed on HEVs, collectively called peripheral lymph node addressin (PNAd), interact with L-selectin expressed on lymphocytes, contributing to the initial step of the lymphocyte homing. In chronic inflammatory states, PNAd is induced on HEV-like vessels but absent in non-lymphoid tissues under normal conditions. Such HEV-like vessels have been observed in various chronic inflammatory diseases including rheumatoid arthritis, lymphocytic thyroiditis, Helicobacter pylori-associated chronic gastritis, and inflammatory bowel disease (IBD), and implicated in lymphocyte recruitment in those diseases. In H. pylori-associated chronic gastritis, PNAd-expressing HEV-like vessels are induced, and the progression of chronic inflammation is highly correlated with appearance of these vessels. Furthermore, eradication of H. pylori by antibiotics resulted in disappearance of PNAd. These results indicate that inhibition of PNAd formation could have therapeutic effect by attenuating lymphocyte recruitment. In ulcerative colitis (UC), PNAd-expressing HEV-like vessels are induced, preferentially in the active phase, and T cells, particularly CD4(+) T cells, are closely associated with these vessels, suggesting that T cell recruitment via PNAd-expressing HEV-like vessels plays at least a partial role in UC pathogenesis. Additionally, N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) is suggested to be a candidate to regulate PNAd induction on HEV-like vessels in UC. These results provide a potential therapeutic strategy to treat UC by blocking T cell adhesion to PNAd-expressing HEV-like vessels. Inhibition or down-regulation of GlcNAc6ST-1 may be an alternative.

Topics: Antigens, Surface; Chronic Disease; Colitis, Ulcerative; Endothelial Cells; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; L-Selectin; Lewis X Antigen; Membrane Proteins; Oligosaccharides; Polysaccharides; Receptors, Lymphocyte Homing; Sialyl Lewis X Antigen; Venules

Helicobacter pylori is a prevalent bacterial, gastroduodenal pathogen of humans that can express Lewis (Le) and related antigens in the O-chains of its surface lipopolysaccharide. The O-chains of H. pylori are commonly composed of internal Le(x) units with terminal Le(x) or Le(y) units or, in some strains, with additional units of Le(a), Le(b), Le(c), sialyl-Le(x) and H-1 antigens, as well as blood groups A and B, thereby producing a mosaicism of antigenic units expressed. The genetic determination of the Le antigen biosynthetic pathways in H. pylori has been studied, and despite striking functional similarity, low sequence homology occurs between the bacterial and mammalian alpha(1,3/4)- and alpha(1,2)-fucosyltransferases. Factors affecting Le antigen expression in H. pylori, that can influence the biological impact of this molecular mimicry, include regulation of fucosyltransferase genes through slipped-strand mispairing, the activity and expression levels of the functional enzymes, the preferences of the expressed enzyme for distinctive acceptor molecules and the availability of activated sugar intermediates. Le mimicry was initially implicated in immune evasion and gastric adaptation by the bacterium, but more recent studies show a role in gastric colonization and bacterial adhesion with galectin-3 identified as the gastric receptor for polymeric Le(x) on the bacterium. From the host defence aspect, innate immune recognition of H. pylori by surfactant protein D is influenced by the extent of LPS fucosylation. Furthermore, Le antigen expression affects both the inflammatory response and T-cell polarization that develops after infection. Although controversial, evidence suggests that long-term H. pylori infection can induce autoreactive anti-Le antibodies cross-reacting with the gastric mucosa, in part leading to the development of gastric atrophy. Thus, Le antigen expression and fucosylation in H. pylori have multiple biological effects on pathogenesis and disease outcome.

Topics: Animals; Carbohydrate Sequence; Fucosyltransferases; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Molecular Sequence Data; Stomach

Topics: Antigens, Bacterial; Bacterial Adhesion; Bacterial Proteins; Clarithromycin; Drug Resistance, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen

Helicobacter pylori (H. pylori) infection is a pathogenic agent of gastric diseases, but their mechanisms are unclear. Effects of ammonia, tumor necrosis factor (TNF), and anti-Lewis autoantibodies induced after H. pylori infection on the development of gastric diseases were investigated. Ammonia disturbed the collagen metabolism in the ulcer base. Soluble TNF receptors regulate the action of TNF. The involvement of anti-Lewis autoantibodies in the development of peptic ulcer might be unlikely. Moreover, H. pylori-specific IgA in gastric juice and TNFalpha gene polymorphism in persons infected with H. pylori were studied. According to H. pylori-specific IgA titer in gastric juice, persons were divided into two histologically and endoscopically different states of disease. TNFA -857 single nucleotide polymorphism (SNP) may be associated with rugal hyperplastic gastritis and gastric carcinomas without severe atrophy. However, complete elucidation of pathogenic mechanisms of H. pylori-induced gastric diseases requires further research.

Topics: Ammonia; Animals; Antibodies; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin A; Lewis Blood Group Antigens; Lewis X Antigen; Peptic Ulcer; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Stomach Diseases; Tumor Necrosis Factor-alpha

Topics: Bacterial Adhesion; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Leukocytes; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides

Expression of cluster of differentiation (CD) antigens changes according to disease status and inflammation. Profiles of CD antigens expression in gastric cancer patients are different based on the status of H. pylori infection.. We conducted this study to profile CD antigen markers in gastric adenocarcinoma cells (AGS cell line) infected with distinct cytotoxin-associated gene A (cagA) genotypes of H. pylori clinical isolates.. The AGS cells were infected with H. pylori isolates with different cagA genotypes, and CD antigens expression was determined using DotScan™ antibody microarray. Formation of "hummingbird" phenotype was determined, and the percentage was calculated.. H. pylori strains harboring cagA upregulated the expression of CD antigen involved in cancer stem cell formation (CD55), but downregulated CD antigens involved in immune regulation (CD40 and CD186) and cell adhesion (CD44). CD54 (neutrophil adhesion) and CD71 (iron transfer) were highly downregulated in the gastric cells infected with Western cagA isolates compared with East Asian isolates. CD antigen expression was different in the cells infected with H. pylori harboring different CagA EPIYA (Glu-Pro-Ile-Tyr-Ala) numbers, in which higher repression of CD54 and CD15 (Lewis x antigen) were observed in the isolate with the highest number of EPIYA motif. Furthermore, higher downregulation of CD15 was observed in the infected gastric cells with high percentage of "hummingbird" phenotype than that of low percentage of "hummingbird" phenotype.. Our study demonstrated the critical roles of CD antigens in the CagA pathogenesis and should be investigated further.

Topics: Amino Acid Motifs; Antigens, Bacterial; Antigens, CD; Antigens, Surface; Bacterial Proteins; Carcinogenesis; Cytotoxins; Helicobacter Infections; Helicobacter pylori; Humans; Iron; Lewis X Antigen; Stomach Neoplasms

In patients with chronic Helicobacter pylori (H pylori) infection, parietal and chief cell atrophy in the gastric corpus, a process known as spasmolytic polypeptide-expressing metaplasia (SPEM), increases the risk for progression to cancer. The relation between H pylori and these metaplastic changes is unclear. We investigated whether H pylori localizes to regions of SPEM.. We developed an in situ adherence assay in which we incubated H pylori with free-floating tissue sections from the gastric corpora of mice; we assessed H pylori distribution along the gastric unit by immunofluorescence. We analyzed the interactions of H pylori with tissue collected from mice with acute SPEM, induced by high-dose tamoxifen. We also evaluated how adhesin-deficient H pylori strains, chemical competition assays, and epithelial glycosylation affected H pylori adhesion to SPEM glands. Mice colonized with the mouse-adapted PMSS1 strain were analyzed for H pylori colonization in vivo during tamoxifen-induced SPEM or after decrease of stomach acid with omeprazole.. Compared with uninjured glands, H pylori penetrated deep within SPEM glands, in situ, through interaction of its adhesin, SabA, with sialyl-Lewis X, which expanded in SPEM. H pylori markedly increased gastric corpus colonization when SPEM was induced, but this proximal spread reversed in mice allowed to recover from SPEM. Decreasing corpus acidity also promoted proximal spread. However, H pylori penetrated deep within corpus glands in vivo only when sialyl-Lewis X expanded during SPEM.. Helicobacter pylori differentially binds SPEM glands in situ and in mice, in large part by interacting with sialyl-Lewis X. Our findings indicate that H pylori expands its niche into the gastric corpus by promoting and exploiting epithelial metaplastic changes that can lead to tumorigenesis.

Topics: Adhesins, Bacterial; Animals; Bacterial Adhesion; Cell Transformation, Neoplastic; Disease Models, Animal; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Intercellular Signaling Peptides and Proteins; Lewis X Antigen; Male; Metaplasia; Mice; Peptides; Sialyl Lewis X Antigen

H. pylori cytotoxin associated antigen A (CagA) plays a significant role in the progression of gastric cancer but their effect on fucosylation to develop gastric cancer is unknown. Fucosyltransferase IV (FUT4) is the key enzyme for synthesis of LewisY (LeY) carried by glycoproteins and glycolipids on the cell membrane. Herein, we compare the expression of CagA, p-EGFR, FUT4 and LeY in gastritis (n = 128, 176), gastric ulcer (n = 174, 213), and gastric cancer (n = 323, 261) tissue and serum samples, respectively by IHC and ELISA. Moreover, we investigated the potential correlation of CagA with FUT4 and LeY overexpression through EGFR activation. IHC and ELISA results showed higher positive cases of H. pylori CagA (83, 86 %), p-EGFR (81, 72 %), FUT4 (91, 97 %) and LeY (93, 92 %) in gastric cancer, compared to gastritis and gastric ulcer, H. pylori CagA (58, 67 & 59, 73 %), p-EGFR (52, 63 & 35, 47 %), FUT4 (68, 78 & 67, 82 %) and LeY (62,76 & 65, 85 %), respectively. We found a significant high expression (H-Value) of CagA (1.79, 1.66), p-EGFR (1.53, 1.58), FUT4 (2.14, 1.66) and LeY (1.69, 1.61) in gastric cancer tissues and serum, respectively as compared to chronic gastritis and gastric ulcers, CagA (0.64,1.14), p-EGFR (0.856, 0.678), FUT4 (0.949,1.197) and LeY (0.68,1.008) (P < 0.0001), respectively. Furthermore, H. pylori CagA showed significant correlation with p-EGFR (R-0.62, -0.74), FUT4 (R-0.81, -0.76) and LeY (R-0.82, -0.70) in gastric tissues and serum (P < 0.0001). H. pylori CagA plays key role in the development of gastric cancer with overexpression of FUT4/LeY, serve as potentially correlative biomarkers of H. pylori CagA associated gastric cancer.

Topics: Biomarkers, Tumor; Female; Fucosyltransferases; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Oligosaccharides; Stomach Neoplasms

High endothelial venule (HEV)-like vessels have been observed in gastric B cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma), as well as in its preceding lesion, chronic Helicobacter pylori gastritis. Previously we reported that glycans on HEV-like vessels in the latter lesion served as L-selectin ligands, although their function is unclear. We have investigated sialyl Lewis X (sLeX)-related glycoepitopes and found that MECA-79(-) /HECA-452(+) /NCC-ST-439(+) HEV-like vessels preferentially mark gastric MALT lymphoma compared to chronic H. pylori gastritis. We then constructed CHO cell lines expressing potential MECA-79(-) /HECA-452(+) /NCC-ST-439(+) glycans, as well as other sLeX-type glycans, on CD34 and evaluated L-selectin binding to those cells, using L-selectin-IgM chimera binding and lymphocyte adhesion assays. L-selectin-IgM chimeras bound to CHO cells expressing 6-sulpho-sLeX attached to core 2-branched O-glycans with or without 6-sulpho-sLeX attached to extended core 1 O-glycans, but only marginally to other CHO cell lines. By contrast, CHO cells expressing 6-sulpho-sLeX attached to extended core 1 and/or core 2-branched O-glycans, as well as non-sulphated sLeX attached to core 2-branched O-glycans, showed substantial lymphocyte binding, while binding was negligible on lines expressing 6-sulpho- and non-sulphated sLeX attached to N-glycans and non-sulphated sLeX attached to extended core 1 O-glycans. These results indicate that MECA-79(-) /HECA-452(+) /NCC-ST-439(+) glycans, specifically, 6-sulpho- and non-sulphated sLeXs attached to core 2-branched O-glycans, expressed on HEV-like vessels in gastric MALT lymphoma function as L-selectin ligands and likely contribute to H. pylori-specific T cell recruitment in the progression of gastric MALT lymphoma.

Topics: Animals; Cell Adhesion; CHO Cells; Cricetinae; Cricetulus; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin M; L-Selectin; Lewis X Antigen; Ligands; Lymphatic Vessels; Lymphocytes; Lymphoma, B-Cell, Marginal Zone; Neoplasm Proteins; Polysaccharides; Sialyl Lewis X Antigen; Stomach Neoplasms

The aim of this study was to investigate the Lewis antigen expression in Helicobacter pylori gastric MALT lymphoma associated strains in comparison to chronic gastritis only strains. Forty MALT strains (19 cagPAI (-) and 21 cagPAI (+)) and 39 cagPAI frequency-matched gastritis strains (17 cagPAI (-) and 22 cagPAI (+)) were included in this study. The lipopolyssacharide for each strain was extracted using a hot phenol method and the expression of Le(x) and Le(y) were investigated using Western Blot. The data were analyzed according to the strains' cagPAI status and vacA genotype. Le(x) was identified in 21 (52.5%) MALT strains and 29 (74.3%) gastritis strains. Le(y) was identified in 30 (75%) MALT strains and 31 (79.5%) gastritis strains. There was an association between cagPAI positivity and Le(x) expression among MALT strains (p<0.0001), but not in gastritis strains (p = 0.64). Among cagPAI (-) strains, isolates expressing solely Le(y) were associated with MALT with an odds ratio of 64.2 (95% CI 4.9-841.0) when compared to strains expressing both Le(x) and Le(y). vacA genotypes did not modify the association between Lewis antigen expression and disease status. In conclusion, cagPAI (-) MALT strains have a particular Lewis antigen profile which could represent an adaptive mechanism to the host response or participate in MALT lymphomagenesis.

Topics: Adult; Bacterial Proteins; Cell Proliferation; Crosses, Genetic; Female; Gastritis; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides; Lymphoma, B-Cell, Marginal Zone; Male; Middle Aged; Virulence

Helicobacter pylori specifically takes up cholesterol and incorporates it into the bacterial membrane, yet little is currently known about cholesterol's physiological roles. We compared phenotypes and in vivo colonization ability of H. pylori grown in a defined, serum-free growth medium, F12 with 1 mg/ml albumin containing 0 to 50 mug/ml cholesterol.. While doubling times were largely unaffected by cholesterol, other overt phenotypic changes were observed. H. pylori strain SS1 grown in defined medium with cholesterol successfully colonized the stomach of gerbils, whereas SS1 grown without cholesterol failed to colonize. H. pylori lipopolysaccharide often displays Lewis X and/or Y antigens. Expression of these antigens measured by whole-cell ELISA was markedly enhanced in response to growth of strain SS1, 26695, or G27 in cholesterol. In addition, electrophoretic analysis of lipopolysaccharide in wild type G27 and in mutants lacking the O-chain revealed structural changes within the oligosaccharide core/lipid A moieties. These responses in Lewis antigen levels and in lipopolysaccharide profiles to cholesterol availability were highly specific, because no changes took place when cholesterol was substituted by beta-sitosterol or bile salts. Disruption of the genes encoding cholesterol alpha-glucosyltransferase or lipid A phosphoethanolamine transferase had no effect on Lewis expression, nor on lipopolysaccharide profiles, nor on the cholesterol responsiveness of these properties. Disruption of the lipid A 1-phosphatase gene eliminated the effect of cholesterol on lipopolysaccharide profiles but not its effect on Lewis expression.. Together these results suggest that cholesterol depletion leads to aberrant forms of LPS that are dependent upon dephosphorylation of lipid A at the 1-position. A tentative model for the observed effects of cholesterol is discussed in which sequential steps of lipopolysaccharide biogenesis and, independently, presentation of Lewis antigen at the cell surface, depend upon membrane composition. These new findings demonstrate that cholesterol availability permits H. pylori to modify its cell envelope in ways that can impact colonization of host tissue in vivo.

Topics: Animals; Cholesterol; Culture Media; Female; Gene Silencing; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Lewis Blood Group Antigens; Lewis X Antigen; Lipid A; Lipopolysaccharides; Stomach

This study tested whether there were different expressions of gastric Lewis antigens between children and adults with Helicobacter pylori infection, and whether the difference was related to the infection outcome. About 68 dyspeptic children and 110 dyspeptic adults were enrolled to check H. pylori infection, its colonization density, and the related histology. Gastric Lewis antigens b (Le(b)), x (Le(x)), and sialyl-Lewis x (sialyl-Le(x)) were immunohistochemically stained and scored for the intensity. The H. pylori-infected adults, but not the children, had a lower Le(b) intensity over the antrum (p=0.019) but higher Le(b) intensity over the corpus (p=0.001) than the non-infected ones. Over the antrum, both the H. pylori-infected children and adults had a lower Le(x) and higher sialyl-Le(x) intensity than those non-infected ones (p<0.05). The H. pylori-infected adults had a higher bacterial density (p=0.004) and Le(b) intensity (p=0.016) over the corpus than the H. pylori-infected children. For the H. pylori-infected adults, but not children, the corpus had a higher Le(b) (p=0.038) and lower Le(x) (p=0.005) intensity than the antrum. Furthermore, the H. pylori-infected adults expressed a higher Le(b) and had a higher bacterial density than those with weak Le(b) (antrum, p<0.001; corpus, p=0.001). In conclusion, H. pylori infection is associated with the intensity change of Lewis antigen expressions in the stomach. The changes of gastric Lewis antigen expressions are different between adults and children with H. pylori infection, which may exert different H. pylori colonization over the corpus between adults and children.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Colony Count, Microbial; Dyspepsia; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Oligosaccharides; Sialyl Lewis X Antigen

Topics: Antibodies, Bacterial; Antigens, Bacterial; Asia; Bacterial Proteins; Demography; Europe; Gastric Mucosa; Genetic Markers; Helicobacter Infections; Helicobacter pylori; Humans; Latin America; Lewis Blood Group Antigens; Lewis X Antigen; North America

Previous studies have shown that the LPS of Helicobacter pylori isolated from North American and European hosts predominantly expresses type 2 Lewis x (Le(x)) and Le(y) epitopes, whilst the LPS from Asian strains has the capacity to express type 1 Le(a) and Le(b) structures. The aim of this study was to evaluate the expression of Le antigens and the cytotoxin-associated antigen (CagA) by H. pylori isolates from Chile. A total of 38 isolates were screened. The expression of Le antigens and CagA was determined by whole-cell indirect ELISA, using commercially available monoclonal anti-Le and polyclonal anti-CagA antibodies. LPS profiles of H. pylori isolates were assessed by gel electrophoresis and Western blotting. Expression of Le(x) and/or Le(y) epitopes was confirmed in 32/38 isolates (84 %), whilst 9/38 isolates (24 %) expressed type 1 Le(b) blood group determinants, in addition to type 2 Le(x) and Le(y) structures. Six strains (16 %) were non-typeable. The majority of H. pylori strains examined were CagA-positive (83.3 %).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chile; Female; Gastrointestinal Diseases; Gene Expression Regulation, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides; Male; Middle Aged; Oligosaccharides

We tested whether the interaction between host gastric Le(x) antigen and the SabA protein of H. pylori determined gastric colonization density.. A total of 145 H. pylori-infected patients were assessed for their bacterial density and gastric Le(b) and sialyl-Le(x) expression. Their corresponding H. pylori isolates were tested for babA2 and sabA genotype by PCR. The sabA-genopositive PCR products were sequenced to check for mutations affecting SabA expression. The BabA and SabA expressions of each isolate were confirmed by Western blotting.. All 145 H. pylori isolates were babA2-genopositive and expressed BabA. There were 116 (80%) sabA-genopositive isolates, but only 45 (31%) of the isolates expressed SabA. Sequence of sabA-genopositive PCR products was achieved in 92 isolates, of which 60% had regular CT repeat-pairs and the other 40% had a unique deletion of the CT repeats. Neither the deletion nor the different CT repeat-pairs in the sabA region were totally correlated with SabA expression, defined by Western blotting. H. pylori density was higher in those expressing gastric sialyl-Le(x) antigen (which interacts with SabA) (p < 0.001) only in those patients expressing weak or no gastric Le(b) antigen (which would interact with BabA), not in those with evident expression of gastric Le(b) antigen.. In Taiwan, H. pylori isolates are 100% BabA-positive, but only 31% of them express SabA. The interaction between gastric sialyl-Le(x) and SabA of H. pylori determines the colonization density of patients expressing gastric Le(b) weakly or not at all.

Topics: Adhesins, Bacterial; Adult; Aged; Analysis of Variance; Antigens, Bacterial; Bacterial Adhesion; Base Sequence; Cohort Studies; Female; Gastric Mucosa; Gene Expression Regulation, Bacterial; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Molecular Sequence Data; Probability; Sensitivity and Specificity; Stomach

Helicobacter pylori extrudes protein- and lipopolysaccharide-enriched outer membrane vesicles from its cell surface which have been postulated to act to deliver virulence factors to the host. Lewis antigen expression by lipopolysaccharide of H. pylori cells has been implicated in a number of pathogenic roles. The aim of this study was to further characterize the expression of lipopolysaccharide on the surface of these outer membrane vesicles and, in particular, expression of Lewis antigens and their association with antibody production in the host.. H. pylori strains were examined for outer membrane vesicle production using transmission electron microscopy and Lewis antigen expression probed using immunoelectron microscopy. Sera from patients were analyzed for cross-reacting anti-Lewis antibodies and, subsequently, absorbed using outer membrane vesicle preparations to remove the cross-reacting antibodies.. The formation of outer membrane vesicles by H. pylori was observed in both in vitro and in vivo samples. Furthermore, vesicles were produced following culture in either liquid or solid medium by all strains examined. Moreover, we observed the presence of Lewis epitopes on outer membrane vesicles using immunoelectron microscopy and immunoblotting. Circulating anti-Lewis antibodies were found in the sera of gastric cancer patients but not in the sera of H. pylori-negative control subjects. Absorption of patient sera with outer membrane vesicles decreased the levels of anti-Lewis autoantibodies.. Our results demonstrate the ability of H. pylori to generate outer membrane vesicles bearing serologically recognizable Lewis antigens on lipopolysaccharide molecules which may contribute to the chronic immune stimulation of the host. The ability of these vesicles to absorb anti-Lewis autoantibodies indicates that they may, in part, play a role in putative autoimmune aspects of H. pylori pathogenesis.

Topics: Antibodies, Bacterial; Autoimmunity; Cell Wall; Electrophoresis, Polyacrylamide Gel; Epitopes; Helicobacter Infections; Helicobacter pylori; Lewis Blood Group Antigens; Lewis X Antigen; Microscopy, Electron; Stomach Neoplasms

In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Le(x)) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Le(x)-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant binding of the parent strain was observed in only 8 out of 22 sections; in four out of eight patients, the Le(x)-negative mutant bound less well. One of these four patients displayed no gastric abnormalities, and the other three showed dysplasia, metaplasia, and adenocarcinoma, respectively; hence, we are unable to define the circumstances under which LPS-mediated adhesion takes place. We conclude that H. pylori LPS plays a distinct but minor role in adhesion.

Topics: Bacterial Adhesion; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Lewis X Antigen; Lipopolysaccharides

We tested if host gastric Lewis antigens and the babA2 genotype of Helicobacter pylori correlated with clinicohistological outcome.. We enrolled 188 dyspeptic patients (45 with duodenal ulcer, 45 with gastric ulcer, and 98 with chronic gastritis) with H pylori infection, proved by culture and gastric histology, reviewed by the updated Sydney system. Gastric expression of Lewis (Le) antigens Le(a), Le(b), Le(x), and Le(y) was determined immunochemically to determine intensity (range 0-3). The corresponding 188 H pylori isolates were screened for babA2 genotype by polymerase chain reaction.. All H pylori isolates had a positive babA2 genotype. We identified Le(a) in 33.5%, Le(b) in 72.9%, Le(x) in 86.2%, and Le(y) in 97.4% of biopsies from these 188 patients. Patients who expressed Le(b) had a higher H pylori density than those who did not express Le(b) (p<0.001). Among 139 patients who expressed Le(b), H pylori density increased with a higher Le(b) intensity (p<0.05). Gastric atrophy decreased with Le(b) intensity and thus resulted in lower H pylori density in the antrum (p<0.05). For the 49 patients without gastric Le(b) expression, H pylori density was positively related with Le(x) and Le(a) expression (p<0.05).. Taiwanese H pylori isolates are 100% babA2 genopositive. Gastric Le(b) as well as Le(x) intensity may be major determinants of H pylori density. While lacking gastric Le(b) expression, Le(x) and Le(a) were closely related to H pylori colonisation.

Topics: Adhesins, Bacterial; Adult; Atrophy; Bacterial Adhesion; Base Sequence; Carrier Proteins; Colony Count, Microbial; Dyspepsia; Female; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Polymerase Chain Reaction; Prevalence; Pyloric Antrum; Taiwan

Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.

Topics: Adhesins, Bacterial; Amino Acid Sequence; Animals; Bacterial Adhesion; Carbohydrate Sequence; Carrier Proteins; Gastric Mucosa; Gastritis; Genes, Bacterial; Glycoconjugates; Helicobacter Infections; Helicobacter pylori; Humans; Lewis X Antigen; Macaca mulatta; Mice; Mice, Transgenic; Molecular Sequence Data; Oligosaccharides; Sialic Acids; Sialyl Lewis X Antigen

The attachment of the bacterial pathogen Helicobacter pylori (H. pylori) to gastric epithelial cells is commonly believed to be required for an efficient and persistent colonization of the human stomach as well as for host cell trans-membrane signaling. In the past, several putative adhesins were postulated, including the outer membrane proteins AlpAB and the bacterial lipopolysaccharide (LPS) presenting oligomeric Lewis x (Le(x)) sugar components. We investigated the AlpAB-mediated and the Le(x)-dependent binding by knockout mutagenesis in one distinct strain, H. pylori P1. We show here that the mutagenesis of either alpA and/or alpB dramatically reduced the adherence of H. pylori P1 to a given gastric biopsy section. None of these mutations influenced the surface exposure of the Le(x) antigen, suggesting that the assembly and/or presentation of LPS is independent of the AlpAB outer membrane proteins. However, a truncation of the LPS O-side chain by a galE mutation abolished the presentation of the Le(x) epitope. This Le(x)-negative strain did not show any significant reduction in its binding capacity to the gastric tissue, when compared with the corresponding wild-type strain. From these data we conclude that the AlpAB-specific adherence is independent of the composition of the LPS and that the oligomeric Le(x) structure does not confer binding to the gastric biopsy material used in this study. As the adhesion properties of our H. pylori strain P1 vary in dependence on the respective biopsy donor it is assumed that the surface-exposed Le(x) epitope recognizes a different host cell receptor than AlpAB, which was probably not present in the tissue sections used in this study.

Topics: Adhesins, Bacterial; Bacterial Adhesion; Bacterial Outer Membrane Proteins; Blotting, Western; DNA, Bacterial; Fluorescent Antibody Technique; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; In Vitro Techniques; Lewis X Antigen; Mutagenesis; Polymerase Chain Reaction; Stomach Diseases

The population dynamics of Helicobacter pylori during colonization in an infected animal host provide a quantifiable experimental model of in vivo microbial phenotype evolution. Phenotype variability in H. pylori populations can be typed as polymorphic expression of Lewis antigens on their cell surfaces. The high mutational frequency of H. pylori for Lewis expression provides substrate for differential selection by the host. Experimental challenge and successful colonization of mice and gerbils allows tracking of H. pylori phenotype variability from the initial inoculation to the ultimate establishment of a quasispecies. Colonization data provide a quantitative experimental model of phenotype evolution in a relatively large population (>10(4) individuals) over a relatively long evolutionary time scale (>10(3) generations). A mathematical model is developed to interpret the data in terms of the dynamic processes occurring during colonization. The mathematical model distinguishes the roles of selection and mutation; quantifies the effects of initial phenotype diversity, mutational frequency, and selective advantage; and applies generally to phenotype evolution in biological populations.

Topics: Animals; Disease Models, Animal; Evolution, Molecular; Female; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides; Mathematical Computing; Mice; Mice, Inbred C3H; Models, Biological; Mutagenesis; Phenotype; Selection, Genetic

Helicobacter pylori strains frequently express Lewis X (Le(x)) and/or Le(y) on their cell surfaces as constituents of the O antigens of their lipopolysaccharide molecules. To assess the effect of Le(x) and Le(y) expression on the ability of H. pylori to colonize the mouse stomach and to adhere to epithelial cells, isogenic mutants were created in which fucT1 alone or fucT1 and fucT2, which encode the fucosyl transferases necessary for Le(x) and Le(y) expression, were deleted. C3H/HeJ mice were experimentally challenged with either wild-type 26695 H. pylori or its isogenic mutants. All strains, whether passaged in the laboratory or recovered after mouse passage, colonized the mice well and without consistent differences. During colonization by the mutants, there was no reversion to wild type. Similarly, adherence to AGS and KatoIII cells was unaffected by the mutations. Together, these findings indicate that Le expression is not necessary for mouse gastric colonization or for H. pylori adherence to epithelial cells.

Topics: Animals; Antibodies, Bacterial; Bacterial Adhesion; Epithelial Cells; Female; Fucosyltransferases; Helicobacter Infections; Helicobacter pylori; Intestinal Mucosa; Lewis Blood Group Antigens; Lewis X Antigen; Mice; Mice, Inbred C3H; Mutagenesis; Stomach

Infection with Helicobacter pylori has been associated with induction of autoantibodies that cross-react with the gastric mucosa. There have been discordant reports as to whether or not these autoantibodies arise due to molecular mimicry between H. pylori and host cell antigens on parietal cells. In this study, we investigated whether molecular mimicry by H. mustelae causes autoantibodies in infected ferrets. Serum from H. mustelae-infected ferrets reacted with parietal cells in the ferret gastric mucosa but not with duodenal or colonic mucosa. These sera did not react with the blood group A epitope on erythrocytes or H. mustelae lipopolysaccharide, and absorption with H. mustelae whole cells or red blood cells did not remove autoantibodies. In conclusion, ferrets naturally infected with H. mustelae generate antibodies that react with parietal cells, but these autoantibodies are not due to molecular mimicry.

Topics: ABO Blood-Group System; Animals; Antibodies, Bacterial; Autoantibodies; Ferrets; Gastric Mucosa; Gastritis, Atrophic; H(+)-K(+)-Exchanging ATPase; Helicobacter Infections; Lewis X Antigen; Lipopolysaccharides; Rabbits

In this study, we found Lewis X (Le(x)) determinants on 68% of Helicobacter pylori isolates from patients with chronic gastroduodenal diseases. Anti-Le(x) IgG were detected more frequently in the sera from dyspeptic children and adults (45 and 46%), with or without proved (culture) H. pylori infection, than in the sera from healthy individuals (14% and 25%). In contrast, the prevalence of anti-Le(x) IgM was higher in the groups of healthy individuals than in the groups of dyspeptic patients. Moreover, anti-Le(x) monoclonal antibody of IgM class enhanced the uptake of Le(x)(+) but not Le(x)(-) H. pylori isolates by phagocytes. In the sera from some dyspeptic patients, we detected Le(x)-anti-Le(x) IgG immune complexes (Le(x) ICs). There was a great difference between children and adults as regards the presence of Le(x) ICs. The immune complexes were found in the sera from nine out of 29 (27%) H. pylori-infected and three out of eight (37%) uninfected adult dyspeptic patients. In comparison, Le(x)-anti-Le(x) IgG ICs were detected only for two out of 18 (11%) H. pylori-infected children. Le(x) ICs were not found in the sera from healthy individuals. Our results suggest that anti-Le(x) IgM may play a protective role in H. pylori infections. In contrast, anti-Le(x) IgG and particularly Le(x)-anti-Le(x) IgG ICs might contribute to the pathogenesis of chronic H. pylori infections.

Topics: Adolescent; Adult; Aged; Antigens, Bacterial; Bacterial Proteins; Child; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Lewis X Antigen; Middle Aged; Peptic Ulcer; Phagocytosis

Lipopolysaccharides of Helicobacter pylori have an antigenic structure that mimics Lewis X occurring in gastric mucosa. The pathogenic role of antigenic mimicry in H. pylori-induced gastritis has been of recent interest. The aim of this study was to examine the relevance of anti-Lewis X antibody in the development of atrophic gastritis in H. pylori infection.. A total of 72 patients were studied. Serum samples were collected to measure IgG antibodies to H. pylori, CagA, VacA and Lewis X. Biopsy specimens were obtained from the antrum and the corpus to examine the grade and the type of atrophic gastritis.. Mean anti-Lewis X antibody titres were higher in 38 VacA-seropositive patients than in 13 seronegative patients (P < 0.05). The difference was not significant between patients with diffuse-type atrophic gastritis and those with multi-focal type. No significant correlation was observed between the titre of anti-Lewis X antibody and the grade of glandular atrophy, whereas CagA seropositivity was associated with glandular atrophy.. Anti-Lewis X antibody may play a role in persistent gastric inflammation, particularly in VacA-seropositive H. pylori infection. However, anti-Lewis X antibody does not seem itself to be associated with atrophic gastritis in patients with H. pylori infection.

Topics: Antibodies; Antibodies, Anti-Idiotypic; Antigens, Bacterial; Bacterial Proteins; Enzyme-Linked Immunosorbent Assay; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Lewis X Antigen

Lipopolysaccharides of Helicobacter pylori have an antigenic structure that mimics Lewis X occurring in gastric mucosa. The pathogenic role of antigenic mimicry in Helicobacter pylori-induced gastritis has been of recent interest.. To examine whether this molecular mimicry affects gastric mucosal inflammation in patients infected with Helicobacter pylori.. A total of 59 patients (mean age 58.0 years, 35 males, 24 females) were studied.. Serum samples were collected to measure IgG antibodies to Helicobacter pylori and Lewis X. Biopsy specimens were obtained from the antrum and corpus for the grading of gastritis. Correlation coefficients between serum Lewis X antibody titre and histological grades of inflammatory infiltration were determined.. There was no significant correlation between anti-Lewis X antibody titre and the grade of mononuclear or polymorphonuclear cell infiltration. High titre of anti-Lewis X antibody was seen only in patients who had increased inflammatory infiltration in the corpus.. Serum anti-Lewis X antibody, possibly induced by Helicobacter pylori infection, does not seem to play a major role in gastric mucosal inflammation in patients with Helicobacter pylori infection.

Topics: Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lewis X Antigen; Male; Middle Aged; Molecular Mimicry

Although Helicobacter pylori express Lewis antigens as a component in the lipopolysaccharide, their role in the infectious process is not well understood. Lewis antigen expression with growth phase was investigated, as well as the distribution of Lewis antigens among isolates from asymptomatic and symptomatic individuals. Lewis antigens are expressed by H. pylori in a growth phase-dependent manner, with the greatest expression occurring in the logarithmic phase of growth. As growth proceeds, an increasing amount of Lewis antigens are shed into the culture supernatant. Lewis antigen expression among H. pylori isolates from asymptomatic individuals is characterized by an absence of type I Lewis antigens, a decrease in Le(x) expression, and an increase in nontypeable H. pylori, as compared with that among H. pylori isolates from symptomatic patients. The data support a role for Lewis antigens in the pathogenesis associated with symptomatic H. pylori infection in colonized individuals.

Topics: Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides; Oligosaccharides; Reference Values

Lewis (Le) antigens have been implicated in the pathogenesis of atrophic gastritis and gastric cancer in the setting of Helicobacter pylori infection, and H. pylori-induced anti-Le antibodies have been described that cross-react with the gastric mucosa of both mice and humans. The aim of this study was to examine the presence of anti-Le antibodies in patients with H. pylori infection and gastric cancer and to examine the relationships between anti-Le antibody production, bacterial Le expression, gastric histopathology, and host Le erythrocyte phenotype. Anti-Le antibody production and H. pylori Le expression were determined by enzyme-linked immunosorbent assay, erythrocyte Le phenotype was examined by agglutination assays, and histology was scored blindly. Significant levels of anti-Le(x) antibody (P < 0.0001, T = 76.4, DF = 5) and anti-Le(y) antibody (P < 0.0001, T = 73.05, DF = 5) were found in the sera of patients with gastric cancer and other H. pylori-associated pathology compared with H. pylori-negative controls. Following incubation of patient sera with synthetic Le glycoconjugates, anti-Le(x) and -Le(y) autoantibody binding was abolished. The degree of the anti-Le(x) and -Le(y) antibody response was unrelated to the host Le phenotype but was significantly associated with the bacterial expression of Le(x) (r = 0.863, r(2) = 0.745, P < 0.0001) and Le(y) (r = 0.796, r(2) = 0.634, P < 0.0001), respectively. Collectively, these data suggest that anti-Le antibodies are present in most patients with H. pylori infection, including those with gastric cancer, that variability exists in the strength of the anti-Le response, and that this response is independent of the host Le phenotype but related to the bacterial Le phenotype.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Autoantigens; Autoimmunity; Chronic Disease; Female; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Immunophenotyping; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Stomach Neoplasms

Helicobacter pylori attach to the gastric mucosa with adhesin, which binds to Lewis b (Le(b)) or H type I carbohydrate structures. The Secretor (Se) gene and Lewis (Le) gene are involved in type I Le antigen synthesis. The present study was performed to investigate the possibility that Se and Le gene polymorphisms alter the risk of H. pylori infection. Two hundred thirty-nine participants were genotyped for Se and Le and tested for the presence of anti-H. pylori IgG antibodies. Using the normal gastric mucosa from 60 gastric cancer patients, we assessed immunohistochemically whether type I Le antigen expression depended on the Se and Le genotypes. The H. pylori infection rate was positively associated with the number of Se alleles (se/se group, 45.1%; Se/se group, 64.6%; and Se/Se group, 73.3%) and negatively associated with the number of Le alleles (le/le group, 76.4%; Le/le group, 68.3%; and Le/Le group, 55.6%). When the subjects were classified into three groups [low risk, (se/se, Le/Le) genotype; high risk, (Se/Se, le/le), (Se/Se, Le/le), and (Se/se, le/le) genotypes; moderate risk, other than low- or high-risk group], the odds ratio relative to the low-risk group was 3.30 (95% confidence interval, 1.40-7.78) for the moderate-risk group and 10.33 (95% confidence interval, 3.16-33.8) for the high-risk group. Immunohistochemical analysis supported the finding that Se and Le genotypes affected the expression of H. pylori adhesin ligands. We conclude that Se and Le genotypes affect susceptibility to H. pylori infection.

Topics: Adult; Aged; Antibodies, Bacterial; Asian People; Enzyme-Linked Immunosorbent Assay; Female; Fucosyltransferases; Galactoside 2-alpha-L-fucosyltransferase; Gastric Mucosa; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Immunohistochemistry; Japan; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Prevalence; Risk Factors; Stomach Neoplasms

We have investigated the possibility that the same patients may be colonized by Helicobacter pylori strains of different genotypes or phenotypes in the antrum as compared to in the duodenum. The strains were typed for DNA fingerprints, different lipopolysaccharides (LPS), and Lewis antigen expression on the O-side chains of LPS.. Polymerase chain reaction (PCR) amplifications using primer sequences (i.e., the Enterobacterial Repetitive Intergenic Consensus [ERIC]) and randomly amplified polymorphic DNA (RAPD) elements were performed to asses chromosomal DNA diversity between H. pylori strains. The expression of different LPS types and Lewis antigens in the various H. pylori isolates were determined by whole bacterial enzyme-linked immunosorbent assays using monoclonal antibodies.. Duodenal ulcer patients had different H. pylori genotypes in the duodenum as compared to in the antrum as shown by ERIC-PCR (44%) and by RAPD-PCR (75%). Different DNA patterns were found among the strains that were isolated from various regions of the duodenum in 4 of 16 patients (25%) as shown by ERIC-PCR and in 8 of 16 patients (50%) as shown by RAPD-PCR. Sixty-three percent of the duodenal ulcer patients had H. pylori strains with a different Lewis antigen phenotype in the duodenum as compared to in the antrum, and 3 of 16 patients (19%) had strains with different Lewis antigens expressed by strains from different duodenal biopsies from the same patient.. The results suggest that a mixed population of different H. pylori strains with marked variation, both genotypically and phenotypically, colonize the same patient.

Topics: DNA Fingerprinting; DNA, Bacterial; Duodenal Ulcer; Enzyme-Linked Immunosorbent Assay; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides; Male; Middle Aged; Phenotype; Pyloric Antrum; Random Amplified Polymorphic DNA Technique

Anomalous Lewis(a) antigen and sulfomucin expression are considered as markers of progression in precursor lesions of gastric cancer. Additionally, Lewis antigen and secretor phenotype have been related to Helicobacter pylori infection and gastric epithelial damage. The two objectives of this study were to correlate Lewis antigen alterations with histochemical changes and to explore the relationship between Lewis and secretor phenotypes and gastric epithelial damage related to H. pylori infection. The study subjects were selected from a chemoprevention trial in Tachira State, Venezuela, an area with a high risk of gastric cancer. Anomalous Lewis(a) antigen expression in Lewis (a-b+) phenotype individuals was closely related to the severity of the histological lesions, especially to dysplasia and type III intestinal metaplasia lesions. A weak relationship was observed between nonsecretor individuals and more advanced lesions of IM, but this association was not statistically significant. There was no relationship between secretor phenotype and H. pylori status, atrophy, regenerative activity, erosion, or ulcer.

Topics: Adult; Aged; Biomarkers, Tumor; Disease Progression; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Lewis X Antigen; Male; Middle Aged; Phenotype; Risk Factors; Stomach Neoplasms

The influence of lipopolysaccharide (LPS) O-polysaccharide chain production on the colonisation ability of Helicobacter pylori in four mouse models (NMRI, C57BL/6, CBA/Ca, and BALB/cA mice) was studied. H. pylori strains that produced smooth-form LPS (S-LPS) detectable in silver-stained electrophoretic gels colonised mice. In contrast, a laboratory-passaged strain G50 and the culture collection strain CCUG 17874 did not colonise mice; the former strain produced low amounts of O-chains only detectable in immunoblotting but not in silver-stained gels, whereas the latter produced rough-form LPS (R-LPS) without O-chains. Furthermore, a galE isogenic mutant, which produced R-LPS, did not colonise mice. However, after repeated broth culture, strains G50 and CCUG 17874 produced S-LPS detectable in silver-stained gels and were capable of colonising mice. Consistent with the production of O-chains, all colonising strains produced Lewis (Le) antigens, Le(x) and/or Le(y). Except for low expression of Le(y) by non-colonising G50, reflecting low production of O-chains, all other non-colonising strains and the galE mutant lacked expression of Le antigens consistent with their production of R-LPS. Lectin typing of strains supported these findings, and also showed that lectin types did not differ before and after colonisation. The low level of O-chain production and Le antigen expression by the non-colonising G50 may not be sufficient to aid colonisation. Examination of protein profiles of H. pylori strains before inoculation showed that protein expression was not significantly different between colonising and non-colonising strains. These results show that S-LPS production with O-chain expression is required by H. pylori for colonisation in a number of mouse models and that care should be taken with inoculating H. pylori strains that loss of O-chains does not occur during subculturing.

Topics: Animals; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Lectins; Lewis X Antigen; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; O Antigens

Populations of Helicobacter pylori cells show a stable expression of Lewis surface antigens, although phase variation may occur among individual organisms grown in vitro. We searched for variation in Lewis phenotypes among H. pylori cells of minimally in vitro-passaged isolates. Lewis expression in 180 clonal H. pylori populations from the primary culture of 20 gastric biopsy samples from 12 patients, and that in 160 isolates from primary cultures from 16 experimentally infected rodents, were examined by enzyme immunoassays. Substantial differences in Lewis expression were found among the isolates from 9 (75%) of 12 patients. These differences were unrelated to overall genetic diversity as determined by polymerase chain reactions for random amplified polymorphic DNA or cagA status, and they persisted during subsequent in vitro passage. In contrast, Lewis expression was highly uniform in H. pylori isolates from different rodents infected for up to 20 weeks. Variation in H. pylori Lewis expression in genetically closely related organisms in human subjects may provide a pool of bacterial phenotypes for the continuous selection of optimally host-adapted populations suitable for persistence.

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Female; Gene Expression Regulation, Bacterial; Genotype; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Mice; Phenotype; Polymerase Chain Reaction; Polymorphism, Genetic; Stomach

We examined whether anti-Lewis x (Le(x)) and y (Le(y)) autoantibodies affect the pathogenesis of Helicobacter pylori-induced peptic ulcers. Of 11 patients with peptic ulcers, 10 patients had both anti-Le(x) and -Le(y) immunoglobulin G (IgG) antibodies, and 1 patient had only anti-Le(x) antibody. After successful eradication, we measured the serum titer of anti-Le(x) and -Le(y) antibodies. Six patients had a reduction of the titers of anti-Le(x) and/or -Le(y) antibodies, whereas no notable changes were detected in 5 patients in the follow-up. This result suggests that anti-Le(x) and -Le(y) autoantibodies had no critical role in the development of H. pylori-induced peptic ulcer.

Topics: Autoantibodies; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides; Peptic Ulcer; Recurrence

Helicobacter pylori infection induces autoantibodies that cross-react with human gastric mucosa from infected individuals. Candidates for the antigens responsible for molecular mimicry causing autoreactivity include the heat-shock protein HspB (Hsp60, sometimes called Hsp54) or Lewis x and Lewis y carbohydrate antigens.. Our goal was to investigate the involvement of HspB (Hsp60) in autoreactivity between H. pylori and gastric biopsy tissue.. Immunoelectron microscopy was used to study cross-reactivity among biopsy tissues from a patient with gastritis, gastric ulcer, and duodenal ulcer and his own serum as well as reactivity with serum raised against HspB from H. pylori and monoclonal antibodies against Lewis antigens.. The patient serum reacted with gastric mucosa, and the antibodies involved were predominantly IgG. Antibody raised to H. pylori HspB (Hsp60) reacted only with H. pylori cells but not with gastric mucosal tissue. In contrast, monoclonal antibodies specific for Lewis x and Lewis y antigens reacted with both H. pylori and human gastric epithelial tissue.. Hsp60 (Hsp54) is unlikely to be involved in autoreactivity seen in individuals infected with H. pylori. In contrast, we could not rule out the role of Lewis x and Lewis y carbohydrate antigens, expressed as a component of H. pylori lipopolysaccharides, in molecular mimicry and autoantibody production.

Topics: Adult; Antigens, Bacterial; Autoantibodies; Autoimmunity; Chaperonin 60; Cross Reactions; Duodenal Ulcer; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Microscopy, Immunoelectron; Molecular Mimicry; Stomach Ulcer

A role of autoimmune processes in the pathology of Helicobacter pylori infections has been suggested. The Lewis determinants present in LPS molecule of H. pylori bacteria have been indicated as the cause of antigenic mimicry. In this study, the prevalence of IgM and IgG antibodies to Lewis X antigen in the sera from children and adults, with or without dyspepsia, infected or not infected with H. pylori, seropositive and seronegative for anti-H. pylori IgG were determined immuno-enzymatically (ELISA). Our results revealed that humans may produce anti-Lewis X antibodies, particularly of IgM class, in the absence of H. pylori infection or H. pylori independent dyspepsia. The production of such antibodies, by healthy children who had never been infected with H. pylori suggested that anti-Lewis X antibodies may occur naturally.

Topics: Adolescent; Adult; Aged; Autoantibodies; Child; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Immunoglobulin M; Lewis X Antigen; Middle Aged

A molecular similarity of Lewis antigens expressed by Helicobacter pylori bacteria and those present in human gastric mucosa has been recognised as a cause of autoimmunity involved in the pathogenesis of chronic type B gastritis and gastric and duodenal ulcers. In this study, the expression of Lewis X determinants was found on 56% of H. pylori strains isolated from patients with chronic gastritis/gastroduodenitis. Anti-Lewis X IgG as well as Lewis X-anti-Lewis X IgG complexes were detected in the sera from patients and even more frequently in the sera from healthy blood donors producing antibodies against surface antigens of H. pylori. It suggested that the initial H. pylori-induced lesions were independent of anti-Lewis X antibody production. When H. pylori bacteria expressing Lewis X antigen were treated with anti-Lewis X monoclonal antibody (mAb) of IgM isotype, they were more susceptible to ingestion by polymorphonuclear leukocytes (PMN) than untreated bacteria. This fact may lead us to believe that anti-Lewis X antibody limits the growth of H. pylori on gastric mucosa.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Antigen-Antibody Complex; Child; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin M; Lewis X Antigen; Middle Aged

Autoantibodies against gastric epithelial cells are detectable in up to 50% of patients with chronic, active Helicobacter pylori gastritis. Presence of autoantibodies against canalicular structures within human parietal cells (anticanalicular autoantibodies) correlate with gastric mucosa atrophy. It has been suggested, that molecular mimicry between H pylori and the host on the level of Lewis X and Lewis Y blood group antigens leads to these autoantibodies. This study aimed at analysing whether antigastric antibodies can be absorbed to Lewis X or Y positive H pylori strains. Sera from 14 H pylori infected patients with anticanalicular autoantibodies were effectively absorbed to H pylori. Immunohistochemical studies of the absorbed sera showed no decrease of antigastric autoreactivity. Pathogenic mechanisms other than molecular mimicry lead to the formation of antigastric autoantibodies, and epitopes other than Lewis antigens are the autoimmune targets.

Topics: Autoantibodies; Chronic Disease; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Molecular Mimicry

Topics: Animals; Apoptosis; Disease Models, Animal; Escherichia coli Proteins; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Lewis Blood Group Antigens; Lewis X Antigen; Lymphocytes; Transcription Factors

Helicobacter pylori is found within the gastric mucous gel layer and in association with the epithelial surface. The aim of this study was to determine the effect of H. pylori infection on mucin gene expression (MUC6, MUC5, and MUC1) in the gastric epithelium.. Gastric biopsy specimens were examined by immunohistochemistry and in situ hybridization for mucin gene expression.. MUC6 was limited to mucous glands of H. pylori-negative patients, but 72% of H. pylori-positive patients also expressed MUC6 in surface mucous cells. In contrast, MUC5 mucin was found in significantly fewer surface mucous cells of H. pylori-positive specimens. Carbohydrates recognized by Lewis (Le) X and paradoxical concanavalin A (con A) staining were aberrantly expressed in the surface mucous cells of 16 of 27 and 17 of 23 H. pylori-positive tissues, respectively. Surface Le(b) was present in 26 of 27 H. pylori-positive and 19 of 30 H. pylori-negative tissues. Eradication of H. pylori resulted in reversal of surface MUC5 and MUC6 expression toward normal patterns. Purified gastric mucins of H. pylori-positive patients bound more anti-MUC6 and anti-Le(b) than mucins from H. pylori-negative patients.. The type of mucin that is normally limited to mucous glands is aberrantly expressed in surface mucous cells of H. pylori-positive patients, whereas less of the surface epithelium expresses normal surface-type gastric mucin.

Topics: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Base Sequence; Biopsy; Concanavalin A; DNA; Enzyme-Linked Immunosorbent Assay; Epithelium; Female; Gastric Mucins; Gastric Mucosa; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; In Situ Hybridization; Lewis X Antigen; Male; Middle Aged; Molecular Sequence Data

Lewis antigens occur in human gastric epithelium and in Helicobacter pylori lipopolysaccharide; their expression is polymorphic in both. Autoimmune mechanisms induced by bacterial Lewis expression have been proposed to cause gastritis. The aim of this study was to examine the relationship between bacterial and host gastric Lewis expression, as determined by the erythrocyte Lewis(a/b) phenotype, and between gastric histopathology and bacterial Lewis expression.. H. pylori Lewis expression was determined by enzyme immunoassays, erythrocyte Lewis phenotype was assessed by agglutination tests, and gastric histopathology was scored blindly.. The host Lewis phenotype was (a+b-) in 15, (a-b+) in 34, and (a-b-) in 17 patients, therefore expressing Lewis x, y, or neither as their major gastric epithelial Lewis type 2 antigen. H. pylori from patients with Lewis(a+b-) expressed Lewis x more than y (1147 +/- 143 vs. 467 +/- 128 optical density units [ODU]; P = 0.006), isolates from patients with Lewis(a-b+) expressed Lewis x less than y (359 +/- 81 vs. 838 +/- 96 ODU; P = 0.0001), and isolates from Lewis(a-b-) patients expressed Lewis x and y approximately equally. Gastritis was unrelated to H. pylori Lewis expression.. In mimicking host gastric epithelium, H. pylori cells not only express Lewis x and y, but the relative proportion of expression corresponds to the host Lewis phenotype, suggesting selection for host-adapted organisms.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Erythrocytes; Female; Gastric Mucosa; Gastritis; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Phenotype; Pyloric Antrum

Topics: Antibodies, Bacterial; Antibodies, Monoclonal; Antibody Specificity; Autoantibodies; Bacterial Proteins; Fucosyltransferases; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immune Tolerance; Isoantibodies; Lewis Blood Group Antigens; Lewis X Antigen; Molecular Mimicry; N-Acetyllactosamine Synthase; T-Lymphocytes