Autoimmune gastritis: historical antecedents, outstanding discoveries, and unresolved problems.
The earliest recorded history of autoimmune gastritis can be traced to 1849 in London, when Thomas Addison described "a very remarkable form of anemia" later called pernicious (fatal) anemia (PA). This was followed by the recognition of a gastric mucosal defect suspected to have a nutritional basis, the discovery of the megaloblast that characterized the anemia, the insufficiency of a dietary extrinsic factor characterized as vitamin B12 (cobalamin), and a gastric-secreted intrinsic factor. Treatment with vitamin B12 proved curative. The link between PA and gastritis and atrophy was first confirmed histologically after immediate fixation of the stomach postmortem and later, in the 1940s, by peroral tube biopsy. The causes of gastritis remained enigmatic until the era of autoimmunity, when autoantibodies were detected first to gastric intrinsic factor and then to gastric parietal cells. Hints of a dichotomy in pathogenesis of gastritis were crystallized by the description in 1973 of Type A (Autoimmune) and Type B (later, Bacterial) gastritis. Clarification was enhanced by identification in Type A gastritis of the autoantigen of the parietal cell antibody, by the alpha and beta subunits of gastric H+/K+ ATPase, and by the highly informative experimental murine model of postneonatal thymectomy autoimmune gastritis, and in Type B of the causative role of gastric infection with Helicobacter pylori (H. pylori). A denouement will require a full understanding of (1) the origin and pathogenetic contribution of antibody to intrinsic factor; (2) the connection, if any, between H. pylori infection and Type A autoimmune gastritis; and (3) the genetic contributions to gastritis, whether due to autoimmunity or to H. pylori infection.
Whittingham
Senga
S
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia. Senga.Whittingham@med.monash.edu.au
Mackay
Ian R
IR
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001327:Autoimmune Diseases / Q000209:etiology* / Q000266:history / Q000276:immunology; D001773:Blood Cells / Q000648:ultrastructure; D004195:Disease Models, Animal; D005756:Gastritis / Q000209:etiology / Q000266:history / Q000276:immunology*; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D010295:Parietal Cells, Gastric / Q000378:metabolism; D014805:Vitamin B 12 / Q000502:physiology
D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D014805:Vitamin B 12