NEONATAL INJECTION OF NATIVE PROTON PUMP ANTIGENS INDUCES AUTOIMMUNE GASTRITIS IN MICE

Background a Aims: Autoimmune gastritis is associated with gastric H+, K+-adenosine tripbosphatase (ATPase)-specific autoantibodies (HKAb),Th e (auto)antigen that triggers disease and the pathogenic role of the a utoantibodies are unknown. The aim of this study was to analyze when t hese autoantibodies are produced during autoimmune gastritis in neonat ally thymectomized mice and whether a native H+,K+-ATPase antigen prep aration can induce disease in mice, Methods: Autoantibodies were chara cterized by a novel assay based on immunoprecipitation of a functional H+,K+-ATPase expressed in Xenopus oocytes. Normal mice were injected intraperitoneally with H+,K+-ATPase-enriched gastric membranes in the absence of adjuvant, Results: Conformational autoantibodies recognizin g both H+,K+-ATPase subunits appeared simultanously with the gastric l esions 1 month after thymectomy, Immunization of neonates, but not adu lts, induced a persistent autoimmune gastritis in the body mucosa, cha racterized by lymphocytic infiltrations, loss of parietal and chief ce lls, metaplasia, and H+,K+-ATPase-specific autoantibodies. The histopa thological lesions of this new model are similar to those in humans an d thymectomized mice, Conclusions: The onset of gastritis and autoanti body production parallels the expression of the H+,K+-ATPase during on togeny. Exposure of the neonatal immune system to organ-specific antig ens expressed late after birth induces autoimmune gastritis in adult m ice.