lewis-x-antigen and Gastritis

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

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

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 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

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

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 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

Lewis antigens are expressed by both human gastric epithelial tissue and Helicobacter pylori. We examined Lewis antigens expressed by gastric epithelium and by H. pylori isolated from the corresponding biopsy tissue.. H. pylori Lewis expression was determined by enzyme immunoassays, and immunoelectron microscopy was used to confirm the Lewis antigens on some H. pylori cells and in some biopsy specimens. Histopathology using identical monoclonal antibodies specific for Lewis A, B, X, and Y antigens was used to detect these antigens in 24 gastric biopsy specimens.. We identified Lewis Y in 100%, Lewis X and Lewis B in 95.8%, and Lewis A in 87.5% of biopsy specimens. In H. pylori, 87.5% expressed Lewis Y, 79.2% Lewis X, and 4.2% (one strain) Lewis B. No Lewis A was detected. Antibody specific for Lewis X labeled the bacteria and associated adhesion pedestal. The cagA gene was present in 92% of strains.. There was no direct relationship between Lewis antigen expression by H. pylori and gastric epithelial cells in infected patients. Expression of Lewis X and Lewis Y by H. pylori suggests the possibility of their requirement for establishment and/or maintenance of infection. An immunoelectron micrograph of H. pylori interaction with the gastric epithelial adhesion pedestal suggests a tentative role for Lewis X in the adhesion process.

Topics: Adolescent; Adult; Aged; Antigens, Bacterial; Bacterial Adhesion; Bacterial Proteins; Biopsy; Epithelial Cells; Female; Gastritis; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Microscopy, Immunoelectron; Middle Aged; Phenotype; Stomach

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

To substantiate that incubation with monoclonal antibody CD15 (C3D-1) elicits a distinctive immunoreaction in normal small intestinal Paneth cells, normal and metaplastic Paneth cells along the digestive tract were assessed to determine whether they are also immunoreactive to CD15.. Paneth cells in paraffin wax embedded specimens of normal small intestine, appendix and proximal ascending colon, and from cases of chronic gastritis and ulcerative colitis were investigated immunohistochemically for lysozyme and CD15 antigen expression by means of the avidin-biotin peroxidase complex method.. CD15 antibody reacted with a high proportion of both normal and metaplastic Paneth cells. Paneth cell immunoreactivity to CD15, however, was less intense and less extensive than to antilysozyme antibody, though the latter also stained many other cell types and was more commonly associated with nonspecific background staining.. CD15 seems to be a valuable adjuvant for the study of Paneth cells in the normal and diseased digestive tract. Furthermore, as CD15 has been shown to be involved in activation of phagocytes, its expression in Paneth cells reinforces their proposed role as antimicrobial agents and regulators of the intestinal flora.

Topics: Appendix; Colitis, Ulcerative; Colon; Epithelium; Gastritis; Gastrointestinal Diseases; Humans; Immunohistochemistry; Intestinal Mucosa; Intestine, Small; Lewis X Antigen

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