Murine autoimmune gastritis and the gastric H,K-ATPase: insights from a new model and autoantibody detection system.
Human type A chronic gastritis or autoimmune gastritis (AIG) is associated with gastric H,K-ATPase-specific autoantibodies (HKAb). The pathogenic role of the HKAb and the triggering autoantigen(s) are unknown. In a mouse model, neonatal thymectomy (nTx) induces AIG, which is likely T cell mediated, although HKAb are always present. Our aim is to study the role of the H,K-ATPase in the initiation of AIG. The direct involvement of the H,K-ATPase in the onset of AIG is suggested by the following findings. AIG appears at the age of 1 month in susceptible BALB.D2 mice, i.e. the time at which H,K-ATPase expression reaches adult levels. A new HKAb assay system based on immunoprecipitation of native H,K-ATPase expressed in Xenopus oocytes has revealed that the early lesion is already associated with low titers of HKAb. Injection of gastric membranes, rich in H,K-ATPase, into neonatal BALB.D2 mice without adjuvant induces a persisting AIG. This new model for AIG will provide the means to identify which H,K-ATPase subunit triggers AIG.
Claeys
D
D
Swiss Institute for Experimental Cancer Research, University of Lausanne, Switzerland.
Saraga
E
E
Kraehenbuhl
J P
JP
D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D005756:Gastritis / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology; D013934:Thymectomy
D017506:H(+)-K(+)-Exchanging ATPase