Neonatal injection of native proton pump antigens induces autoimmune gastritis in mice.
OBJECTIVE
Autoimmune gastritis is associated with gastric H+, K(+)-adenosine triphosphatase (ATPase)-specific autoantibodies (HKAb). The (auto) antigen that triggers disease and the pathogenic role of the autoantibodies are unknown. The aim of this study was to analyze when these autoantibodies are produced during autoimmune gastritis in neonatally thymectomized mice and whether a native H+, K(+)-ATPase antigen preparation can induce disease in mice.


METHODS
Autoantibodies were characterized 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 recognizing both H+, K(+)-ATPase subunits appeared simultaneously with the gastric lesions 1 month after thymectomy. Immunization of neonates, but not adults, induced a persistent autoimmune gastritis in the body mucosa, characterized by lymphocytic infiltrations, loss of parietal and chief cells, metaplasia, and H+, K(+)-ATPase-specific autoantibodies. The histopathological lesions of this new model are similar to those in humans and thymectomized mice.


CONCLUSIONS
The onset of gastritis and autoantibody production parallels the expression of the H+, K(+)-ATPase during ontogeny. Exposure of the neonatal immune system to organ-specific antigens expressed late after birth induces autoimmune gastritis in adult mice.
Claeys
D
D
Swiss Institute for Experimental Cancer Research, University of Lausanne, Epalinges, Switzerland.
Saraga
E
E
Rossier
B C
BC
Kraehenbuhl
J P
JP
D000818:Animals; D000831:Animals, Newborn; D000917:Antibody Formation; D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003433:Crosses, Genetic; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009865:Oocytes / Q000502:physiology; D010295:Parietal Cells, Gastric / Q000201:enzymology / Q000276:immunology; D017494:Proton Pumps / Q000276:immunology*; D013552:Swine; D013934:Thymectomy; D014982:Xenopus laevis
D001323:Autoantibodies; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D017494:Proton Pumps