Autoimmune gastritis and H+/K+-ATPase

Autoimmune gastritis, which eventually may develop into pernicious anemia (PA), is an organ-specific autoimmune disease characterized by chronic atrophic corpus gastritis and circulating parietal cell autoantibodies (6,13,21). By means of immunofluorescence and complement fixation techniques the antibodies were shown to react with a microsomal component (11,22) and the antigen was further localized to the microvilli of the parietal cell (10). By using a Western blotting technique and a preparation enriched in the H+/K+-ATPase (EC3.6.1.36), the acid pump of the stomach, this enzyme was suggested to be the autoantigen (12). Later the H+/K+-ATPase was shown to comprise two subunits, the a- and s-subunits, which migrate as 94 kDa and 60–90 kDa components on sodium dodecyl sulphate Polyacrylamide gel electrophoresis (SDS-PAGE) (9,14,19,23). Both the α- and s-subunits of the H+/K+-ATPase have been identified as autoantigens by immunoblotting and immunoprecipitation using parietal cell autoantibodies (7,8,12). The autoantibodies were reported to bind to the cytoplasmic side of the H+/K+-ATPase (18) and the activity of the H+/K+-ATPase was inhibited by the autoantibodies (2). Removal of the N-linked oligosaccharides from the s-subunit of pig H+/K+-ATPase eliminated autoantibody binding (8). The intact disulfide bonds in the s-subunit are essential for gastric H+/K+-ATPase activity (4) and also for autoantibody binding (8). The cDNA of both the α- and s-subunit of the human H+/K+-ATPase were cloned recently (15,16) which made possible the characterization of the antibody epitopes using recombinant DNA technology. The human H +/K+-ATPase s-subunit comprises a 33 kDa core protein with seven possible N-linked glycosylation sites (15).