Immunopathology of autoimmune gastritis: Lessons from mouse models

Autoimmune gastritis in humans is a chronic inflammatory disease of the sto mach accompanied by specific destruction of gastric parietal and zymogenic cells resulting in pernicious anemia. Human gastritis can be accurately rep roduced in mice and is characterised by autoantibodies to the alpha- and be ta-subunits of the gastric H/K ATPase (the enzyme responsible for gastric a cid secretion) and cellular destruction of parietal and zymogenic cells wit hin the gastric gland. Studies with these mouse models have given us our cu rrent concepts of the immunopathogenesis of the gastritis. Mouse models hav e shown that a T cell response is generated to the alpha- and beta-subunits of the H/K ATPase and that an immune response to the beta-subunit seems to be required for disease initiation. Using these models, we have defined ke y events associated with a damaging autoimmune response to the gastric H/K ATPase. The mechanisms associated with the cellular destruction associated with autoimmune gastritis are not know, but may involve signaling through d eath inducing pathways such as the Fas/FasL and TNF/TNFR pathways. This kno wledge should permit us to develop strategies to prevent and treat the gast ritis.