Vitamin B12 – Functions (Andres, et al.; Song, et al.) Methionine synthase No de novo pathway Coupled methylation Methylmalonyl CoA Mutase Generates radicals Produces Succinyl-CoA Free folate Hematopoiesis Nucleic acids
Autoimmune mechanism (Moretti, et al.; Antico, et al.) Anti-intrinsic factor antibodies Intrinsic factor blocking abs Type I Works competitively Fills binding sites Intrinsic factor binding abs Type II Binds with vitamin B12 Causes precipitation
Autoimmune mechanism (Banka, et al.; Torbenson, et al.) Anti-parietal cell antibodies Created during type A gastric infection Dendritic cells present H+/P + -ATPase as Ag Th1 CD 4 + T cells attack α- and β-subunits of H + /P + -ATPase Proton pump (H + out, K + in) Constitute most coating of parietal cells Preexisting due to prior helicobacter pylori infection Affects >50% world pop. Only 20% show symptoms CD 4 + recognizes H+/P + - ATPase as H. pylori Suspected genetic causation - FUT2 gene Makes protein that is distantly involved in H antigen production
Case Studies Patient expecting cancer (Tisman, et al.) Male age 75 at high risk of prostate cancer Active vitamin B12 (IF bound) was depleted before all vitamin B12 Lack of IF bound vitamin B12 can affect DNA synthesis Overall expectation: Increase mutation rate In this case: Retardation of cancer growth possibly due to poor DNA synthesis Patient with chronic fatigue (Kadikoylu, et al.) Female age 55 examined after several months fatigue Detection of multiple factors led to PA diagnosis Further testing led to the diagnosis of a type 1 gastric carcinoid tumor Not generally detected alone Fruitless biopsy Annual follow-up examinations
Pernicious Anemia Malabsorption of vitamin B12 due to lack of parietal cells or intrinsic factor Intrinsic factor – blocking (competition), binding (precipitation) Parietal cells - H + /K + -ATPase ‘confused’ for helicobacter pylori Active vitamin B12 works with methionine synthase, methylmalonyl-CoA mutase, and folate Synthase – methylation of essential amino acid Mutase – uses radicals to make succinyl Co-A (citric acid cycle) Folate – aids maturation of erythrocytes, methylates nucleic acids The exact causes of the autoimmune responses related to PA are unknown Cancers (especially stomach), age-related gastric atrophy, genetics
Literature Cited Andres, E., Serraj, K. 2012. Optical management of pernicious anemia. Dove Medical Press [serial online] 3: 97-103. Antico, A., Tampoia, M., Villalta, D., Tonutti, E., Tozzoli, R., and Bizzaro, N. 2012. Clinical usefulness of the serological gastric biopsy for the diagnosis of chronic autoimmune gastritis. Clinical and Developmental Immunology [serial online] ePub. Banka, S., Ryan, K., Thomson, W., and Newman, W.G. 2011. Pernicious anemia – Genetic insights. Autoimmunity Reviews [serial online] 10(8): 455-459. Kadikoylu, G., Yavasoglu, I., Yukselen, V., Ozkara, E., and Bolamin, Z. 2006. Treatment of solitary gastric carcinoid tumor by endoscopic polypectomy in a patient with pernicious anemia. World Journal of Gastroenterology [serial online] 12(26): 4267-4269. Moretti, R.,Torre, P., Antonello, R.M., Cattaruzza, T., Cazzato, G., Bava, A. 2004. Vitamin B12 and folate depletion in cognition: A review. Neurology India [serial online] 52(3): 310-318. Song, I.C., Lee, H.J., Kim, H.J., Bae, S.B., Lee, K.T., Yang, Y.J., Park, S.Y., Cho, D.Y., Kim, N.Y., Cho, I.S., and Jo, D.Y. 2013. A multicenter retrospective analysis of the clinical features of pernicious anemia in a Korean population. Journal of Korean Medical Science [serial online] 28(2): 200-204. Tisman, G.,Kutik, S., Rainville, C. 2009. Coexistence of pernicious anemia and prostate cancer – ‘an experiment of nature’ involving vitamin B12 modulation of prostate cancer growth and metabolism: a case report. Journal of Medical Case Reports [serial online] 3: 9295. Torbenson, M., Abraham, S.C., Boitnott, J., Yardley, J.H., and Wu, T.T. 2002. Autoimmune gastritis: Distinct histological and immunochemical findings before complete loss of oxyntic glands. Modern Pathology [serial online] 15(2): 102-109. Questions?