Immunologic Research

, Volume 65, Issue 1, pp 326–330 | Cite as

Pathophysiology and laboratory diagnosis of pernicious anemia

  • Ban-Hock Toh
Mechanism in Autoimmunity


Pernicious anemia is the hematologic manifestation of chronic atrophic gastritis affecting the corpus of the stomach that denudes the gastric mucosa of gastric parietal cells. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10–20 years. The gastritis arises from activation of pathologic Th1 CD4 T cells to gastric H/K ATPase that is normally resident on gastric mucosal secretory membranes. The onset of autoimmune gastritis is marked by circulating parietal cell antibody to gastric H/K ATPase. Gastric parietal cells produce two essential biologics: intrinsic factor and HCl acid. Pernicious anemia is a consequence of intrinsic factor loss and neutralizing intrinsic factor antibody that impairs cobalamin absorption. Acid loss leads to iron deficiency anemia that precedes cobalamin-deficient pernicious anemia by 20 years. Laboratory diagnosis rests on parietal cell antibody with or without intrinsic factor antibody, cobalamin-deficient megaloblastic anemia and elevated serum gastrin from loss of acid secretion. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus.


Parietal cell antibody Intrinsic factor antibody Cobalamin Iron deficiency anemia Gastrin 


  1. 1.
    Toh BH, Alderuccio F. Pernicious anaemia. Autoimmunity. 2004;37(4):357–61.CrossRefPubMedGoogle Scholar
  2. 2.
    Toh BH. Diagnosis and classification of autoimmune gastritis. Autoimmun Rev. 2014;13(4–5):459–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med. 1997;337(20):1441–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Toh BH, et al. Cutting edge issues in autoimmune gastritis. Clin Rev Allergy Immunol. 2012;42(3):269–78.CrossRefPubMedGoogle Scholar
  5. 5.
    Alderuccio F, et al. Animal models of human disease: experimental autoimmune gastritis–a model for autoimmune gastritis and pernicious anemia. Clin Immunol. 2002;102(1):48–58.CrossRefPubMedGoogle Scholar
  6. 6.
    Biondo M, et al. Local transgenic expression of granulocyte macrophage-colony stimulating factor initiates autoimmunity. J Immunol. 2001;166(3):2090–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Hershko C, et al. Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood. 2006;107(4):1673–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Lam-Tse WK, et al. The association between autoimmune thyroiditis, autoimmune gastritis and type 1 diabetes. Pediatr Endocrinol Rev PER. 2003;1(1):22–37.PubMedGoogle Scholar
  9. 9.
    Tsirogianni A, Pipi E, Soufleros K. Specificity of islet cell autoantibodies and coexistence with other organ specific autoantibodies in type 1 diabetes mellitus. Autoimmun Rev. 2009;8(8):687–91.CrossRefPubMedGoogle Scholar
  10. 10.
    Ness-Abramof R, et al. Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid disease. Am J Med Sci. 2006;332(3):119–22.CrossRefPubMedGoogle Scholar
  11. 11.
    Burman P, et al. A study of autoimmune gastritis in the postpartum period and at a 5-year follow-up. Gastroenterology. 1992;103(3):934–42.CrossRefPubMedGoogle Scholar
  12. 12.
    Zauli D, et al. Prevalence of autoimmune atrophic gastritis in vitiligo. Digestion. 1986;34(3):169–72.CrossRefPubMedGoogle Scholar
  13. 13.
    De Block CE, De Leeuw IH, Van Gaal LF. Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab. 2008;93(2):363–71.CrossRefPubMedGoogle Scholar
  14. 14.
    Korstanje A, et al. The serological gastric biopsy: a non-endoscopical diagnostic approach in management of the dyspeptic patient: significance for primary care based on a survey of the literature. Scand J Gastroenterol Suppl. 2002;236:22–6.CrossRefGoogle Scholar
  15. 15.
    Iijima K, et al. Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal, healthy stomach. World J Gastroenterol. 2009;15(7):853–9.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Korstanje A, et al. Comparison between serology and histology in the diagnosis of advanced gastric body atrophy: a study in a Dutch primary community. J Clin Gastroenterol. 2008;42(1):18–22.CrossRefPubMedGoogle Scholar
  17. 17.
    Checchi S, et al. Serum ghrelin as a marker of atrophic body gastritis in patients with parietal cell antibodies. J Clin Endocrinol Metab. 2007;92(11):4346–51.CrossRefPubMedGoogle Scholar
  18. 18.
    Suzuki H, et al. Plasma ghrelin concentration correlates with the levels of serum pepsinogen I and pepsinogen I/II ratio—a possible novel and non-invasive marker for gastric atrophy. Hepatogastroenterology. 2004;51(59):1249–54.PubMedGoogle Scholar
  19. 19.
    Chuang JS, et al. Diagnostic ELISA for parietal cell autoantibody using tomato lectin-purified gastric H+/K(+)-ATPase (proton pump). Autoimmunity. 1992;12(1):1–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Sugiu K, et al. Evaluation of an ELISA for detection of anti-parietal cell antibody. Hepatogastroenterology. 2006;53(67):11–4.PubMedGoogle Scholar
  21. 21.
    Toh BH, et al. Parietal cell antibody identified by ELISA is superior to immunofluorescence, rises with age and is associated with intrinsic factor antibody. Autoimmunity. 2012;45(7):527–32.CrossRefPubMedGoogle Scholar
  22. 22.
    Lahner E, et al. Reassessment of intrinsic factor and parietal cell autoantibodies in atrophic gastritis with respect to cobalamin deficiency. Am J Gastroenterol. 2009;104(8):2071–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Khan S, et al. Limited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia. J Clin Pathol. 2009;62(5):439–41.CrossRefPubMedGoogle Scholar
  24. 24.
    Tozzoli R, et al. Autoantibodies to parietal cells as predictors of atrophic body gastritis: a five-year prospective study in patients with autoimmune thyroid diseases. Autoimmun Rev. 2010;10(2):80–3.CrossRefPubMedGoogle Scholar
  25. 25.
    Alonso N, et al. Serum autoimmune gastritis markers, pepsinogen I and parietal cell antibodies, in patients with type 1 diabetes mellitus: a 5-year prospective study. J Endocrinol Invest. 2011;34(5):340–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Medicine, Southern Clinical School, Faculty of Medicine, Nursing and Health SciencesMonash University, and Australian ClinicalabsClaytonAustralia

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