Autoimmune gastritis (AIG) is a chronic inflammation of the stomach mucosa which hinders iron and vitamin B12 uptake and may lead to atrophic gastritis with malabsorption. The stomach mucosa is infiltrated by lymphocytes, plasma cells and granulocytes. Epithelial cells become necrotic, and main and parietal cells are replaced by mucoid cells. As a final stage, atrophy develops over many years. AIG causes a limited production of pepsin, hydrochloric acid and intrinsic factor (IF). Over the course of year, the vitamin B12 deficiency leads to pernicious anaemia (PA). In most patients, AIG remains asymptomatic over many years until reaching advanced stages of atrophy. Symptoms of PA are anaemia, fatigue, light-headedness and tachycardia. Moreover, the vitamin B12 deficiency hinders DNA synthesis, which causes megaloblasts to be formed in the bone marrow and the gastrointestinal epithelium. This results in malabsorption and diarrhoea with weight loss, anorexia, glossitis, icterus and neurological complaints.
AIG is characterised by the presence of autoantibodies against parietal cell antigens (PCA) and IF. IF is a glycoprotein which is secreted by the parietal cells. It forms complexes with vitamin B12, whose absorption in the ileum is hindered by anti-intrinsic factor antibodies (IFA). Sera from AIG or PA patients contain two types of IFA (both IgG). IFA of type 1 react with the vitamin B12 binding site of the IF, IFA of type 2 hinder the binding of the IF to the receptors in the ileum. IFA have a very high specificity for AIG. With PA, IFA occur in 40 to 80 % of patients depending on the disease stage.
Antibodies against PCA occur in patients with AIG as well as PA. They are mainly of the IgG and IgA classes. The prevalence of antibodies against PCA is very high in almost all patients with chronic-atrophic gastritis, amounting to nearly 100 %. Antibodies against PCA also have a very high sensitivity for PA, amounting to 80 to 90 % at the time of diagnosis. Over the course of disease, their prevalence decreases due to the progressing destruction of the parietal cells. With respect to the specificity of the anti-PCA antibodies, it must be taken into account that they can also be detected in patients with endocrinopathies and healthy blood donors.
For very specific determination of APCA, EUROIMMUN has developed the recombinant ATP4B as the new antigen. ATP4B stands for the extracellular domain of the β-subunit of H+/ K+-ATPase and is the main antigen of APCA. The Anti-ATP4B ELISA (IgG) thus yields a significantly higher specificity without a loss in sensitivity compared to the Anti-PCA ELISA (IgG).