Relationship of anti-Lewis x and anti-Lewis y antibodies in serum samples from gastric cancer and chronic gastritis patients to Helicobacter pylori-mediated autoimmunity.
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.
Heneghan
M A
MA
Department of Medicine, Clinical Science Institute, University College Hospital Galway, National University of Ireland, Galway, Ireland.
McCarthy
C F
CF
Janulaityte
D
D
Moran
A P
AP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D005757:Gastritis, Atrophic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016481:Helicobacter Infections / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D016256:Lewis X Antigen / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D001324:Autoantigens; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; C094162:Lewis Y antigen