Pernicious anemia (PA) is a complex, autoimmune, multi-factorial disease. Rapid progress has been made in the understanding of susceptibility to a spectrum of other autoimmune diseases through genome wide association studies (GWAS). However, PA has been conspicuous by its absence from this work. Here, we examine the evidence that PA has a significant heritable component through epidemiological evidence and its co-occurrence with other autoimmune diseases. Further, we consider how knowledge of the genetic susceptibility to other autoimmune diseases may provide insight into the etiology of PA.Researchers have developed murine lymphopenic, non-lymphopenic, transgenic, spontaneous and infectious agent based models to induce an experimental autoimmune gastritis (EAG) for the study of human organ-specific autoimmune disease. These models result in a chronic inflammatory mononuclear cell infiltrate in the gastric mucosa, destruction of parietal and zymogenic cells with autoantibodies reactive to the gastric parietal cells and the gastric H+/K+ ATPase (ATP4), arguably hallmarks of a human autoimmune gastritis (AIG). In the case of AIG, it is well documented that, in addition to parietal cell antibodies being detected in up to 90% of patients, up to 70% have intrinsic factor antibodies with the later antibodies considered highly specific to patients with pernicious anemia. This is the first report specifically investigating the occurrence of intrinsic factor antibodies, cobalamin deficiency and pernicious anemia in EAG models. We conclude, in contrast to AIG, that, in the three EAG models examined, intrinsic factor is not selected as a critical autoantigen.

Cobalamin (vitamin B12) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. Pernicious anemia is generally the cause of cobalamin deficiency in Western populations with an incidence of around 1.9% in persons over 60 years of age. Human autoimmune gastritis (type A chronic atrophic gastritis) is considered the underlying pathological lesion of pernicious anemia. The gastric lesion, confined to the fundus and body of the stomach, is characterized by an inflammatory infiltrate within the gastric mucosa, and the loss of parietal and zymogenic cells from gastric glands. Most patients with pernicious anemia have circulating autoantibodies reactive to ATP4 (the proton pump), present on and in parietal cells (∼ 85%) and to intrinsic factor (∼ 60%). Intrinsic factor, secreted by stomach parietal cells in humans, promotes absorption of cobalamin in the ileum via a specific receptor-mediated endocytosis.

visit for more articles at Journal of Autoimmune Disorders

Kindly submit your article at  https://www.imedpub.com/submissions/autoimmune-disorders.html 

Regards
Mishita
Jornal co-ordinator
Journal of  Autoimmune Disorders