Relationship of anti-Kewis 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 ga stritis and gastric cancer in the setting of Helicobacter pylori infection, and H. pylori-induced anti-Le antibodies have been described that cross-re act 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. pylor i infection and gastric cancer and to examine the relationships between ant i-Le antibody production, bacterial Le expression, gastric histopathology, and host Le erythrocyte phenotype. Anti-Le antibody production and H. pylor i Le expression were determined by enzyme-linked immunosorbent assay, eryth rocyte 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-Ley antibody (P < 0.0001, T = 73.05, DF = 5) were f ound in the sera of patients with gastric cancer and other H. pylori-associ ated pathology compared with H. pylori-negative controls. Following incubat ion 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 signifi cantly associated with the bacterial expression of Le(x) (r = 0.863, r(2) = 0.745, P < 0.0001) and Ley (r = 0.796, r(2) = 0.634, P < 0.0001), respecti vely. Collectively, these data suggest that anti-Le antibodies are present in most patients with H. pylori infection, including those with gastric can cer, that variability exists in the strength of the anti-Le response, and t hat this response is independent of the host Le phenotype but related to th e bacterial Le phenotype.