Pernicious anemia is caused by
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Causes of Pernicious Anemia
Autoimmune Gastritis and Intrinsic Factor Deficiency
Pernicious anemia is primarily caused by an autoimmune response that leads to chronic atrophic gastritis, which in turn results in a deficiency of intrinsic factor. Intrinsic factor is a glycoprotein secreted by the parietal cells of the stomach, essential for the absorption of vitamin B12 (cobalamin) in the terminal ileum. The autoimmune destruction of these parietal cells leads to a lack of intrinsic factor, causing vitamin B12 deficiency and subsequent anemia .
Genetic Susceptibility
Genetic factors also play a significant role in the development of pernicious anemia. Genome-wide association studies have identified several genetic loci associated with an increased risk of the disease. Notable genes include PTPN22, PNPT1, HLA-DQB1, IL2RA, and AIRE, which are involved in immune regulation and have been linked to other autoimmune disorders. This genetic predisposition underscores the autoimmune nature of pernicious anemia.
Helicobacter pylori Infection
Long-standing infection with Helicobacter pylori has been implicated in the pathogenesis of pernicious anemia. The infection can lead to chronic gastritis, which over time may evolve into an autoimmune process that destroys the gastric mucosa, including the parietal cells responsible for intrinsic factor production. This transition from an infectious to an autoimmune etiology highlights the complex interplay between environmental and genetic factors in the development of the disease.
Autoimmune Polyendocrine Syndrome
Pernicious anemia is often part of a broader spectrum of autoimmune disorders, collectively known as autoimmune polyendocrine syndrome. This syndrome includes conditions such as autoimmune thyroid disease, type 1 diabetes, and vitiligo. The presence of these coexisting autoimmune conditions further supports the autoimmune basis of pernicious anemia .
Diagnostic Challenges
Diagnosing pernicious anemia can be challenging due to its diverse clinical presentations and the limitations of current diagnostic tools. Patients may present with a range of symptoms, from classic signs of anemia to neurological manifestations without anemia. The presence of intrinsic factor and parietal cell antibodies serves as a useful diagnostic marker, although the sensitivity and specificity can vary .
Conclusion
Pernicious anemia is a multifactorial disease primarily caused by autoimmune destruction of gastric parietal cells, leading to intrinsic factor deficiency and subsequent vitamin B12 deficiency. Genetic susceptibility, chronic Helicobacter pylori infection, and association with other autoimmune disorders further contribute to its pathogenesis. Despite advances in understanding the disease, diagnostic challenges remain, necessitating a comprehensive approach to diagnosis and management.
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