Immunological aspects of gastritis and pernicious anaemia

Pernicious anaemia (PA) and chronic atrophic gastritis (CAG) aggregate in families, occur more often in women, and are associated with various heritable traits such as fair skin and blue eyes. They are linked to certain HLA types. Linkages are relatively weak for A and B antigens, but somewhat stronger in the case of DR antigens. There are strong associations between PA and other organ-specific autoimmune diseases, particularly those affecting the thyroid. Discordance for PA in monozygotic twins has been reported, and it may well be that expression of the disease requires, in a genetically susceptible individual, initial injury to the gastric mucosa by some environmental agent such as a virus or some physical irritant, with perpetuation of injury then depending upon autoimmune mechanisms. Numbers of T cells are substantially increased in the gastric mucosa of patients with PA, but the ratio of T suppressor to T helper cells is normal. There is a relatively greater increase in numbers of cells not of T lineage, presumably B-cells. Gastric autoantibodies, both to different components of the parietal cell and to two sites on the IF molecule, are present in a majority of patients with PA. There is evidence that these autoantibodies, especially PCA, may be cytotoxic to parietal cells, and may also inhibit their maturation and proliferation. Antibodies to chief cells have not been described, and the parallel disappearance of these cells in atrophic gastritis is unexplained. The peripheral blood lymphocytes of some patients with autoimmune gastritis transform, or produce lymphokines, when exposed to gastric antigens, and patients with PA have been shown to have delayed type cutaneous hypersensitivity to gastric antigens. The relevance of these observations to the pathogenesis of their gastric mucosal lesion is unclear. There is a growing body of evidence to support the operation of humoral immune mechanisms in autoimmune gastritis, but this clearly does not preclude the coexistent involvement of cellular mechanisms. For example, impaired suppressor T cell function has been strongly implicated in certain other autoimmune disorders, but has received scant attention in PA. By generally accepted criteria, PA is an excellent example of an organ-specific autoimmune disease. As yet, there is no acceptable single unifying hypothesis which will account for all of the phenomena which have been described in the disease.(ABSTRACT TRUNCATED AT 400 WORDS)