lewis-y-antigen and Chronic-Disease

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

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