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

Abstract

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.

FIG. 1

Inhibition of binding of commercially available anti-Le^x antibody to Le^x-expressing H. pylori LPS (NCTC 11637) by patient sera of different disease groups before absorption (A) and after absorption (B) with Le^x glycoconjugate. Direct binding of commercial anti-Le^x antibody alone to the LPS was measured (LPS), and the abilities of unabsorbed or absorbed sera from gastric cancer (Cancer), duodenal ulcer (DU), chronic gastritis (Gastr), gastric ulcer (GU), and nonulcer dyspepsia (NUD) patients, as well as from a control group (Cont), to inhibit the binding of the commercial antibody were determined. Excluding the control group, a significant enhancement of binding of the commercially available anti-Le^x antibody was found when absorbed patient sera were tested.

FIG. 2

Inhibition of binding of commercially available anti-Le^y antibody to Le^y-expressing H. pylori LPS (P466) by patient sera of different disease groups before absorption (A) and after absorption (B) with Le^y glycoconjugate by patient sera of different disease groups. Direct binding of commercial anti-Le^y alone to the LPS was measured (LPS), and the abilities of unabsorbed or absorbed sera from gastric cancer (Cancer), duodenal ulcer (DU), chronic gastritis (Gastr), gastric ulcer (GU), and nonulcer dyspepsia (NUD) patients, as well as from a control group (Cont), to inhibit binding of the commercial antibody were determined. Excluding the control group, a significant enhancement of binding of the commercially available anti-Le^x antibody was found when absorbed patient sera were tested.

FIG. 3

Correlation of inhibition of binding of commercial anti-Le^x (A) and anti-Le^y (B) antibodies by the sera of H. pylori-positive patients with bacterial expression of Le^x and Le^y, respectively, on isolates from the same patients.