Intrinsic Factor is a 50-kDA glycoprotein and belongs to the eukaryotic cobalamin transport proteins family. Intrinsic Factor is secreted by the parietal cells of the stomach and is necessary for absorption of Vitamin B12 in the intestines. After exit from the acidic environment from the stomach, B12 is able to bind to Intrinsic Factor and via specific receptor mediated endocytosis in the ileal mucosa the B12 Intrinsic Factor complex enters the portal circulation.
Pernicious anaemia is the most common Vitamin B12 deficiency and is characterised by Vitamin B12 deficiency, megaloblastic anaemia, neuropathy and atrophic gastritis with intrinsic factor autoantibodies. Pernicious anaemia occurs as an end result to an autoimmune disease that destroys the gastric muscosa. First the parietal cells of the stomach, which produce Intrinsic Factor, are depleted. Second autoantibodies to Intrinsic Factor block the binding sites for Vitamin B12.
There are two types of Intrinsic Factor Antibodies. Type 1 (Intrinsic Factor blocking antibodies) which, blocks the binding site on intrinsic factor for Vitamin B12 and type 2 (Intrinsic Factor binding antibodies) which, target a different site on intrinsic factor and prevent the intrinsic factor-Vitamin B12 complex from attaching to the binding sites in the small intestine.
The presence of Intrinsic Factor Antibodies (IFAB) as well as megaloblastic anaemia and low serum vitamin B12 are diagnostic of pernicious anaemia. A positive Intrinsic Factor antibody result can exclude the need for further testing, such as the Schillings test. The following autoimmune disease states are associated with pernicious anaemia and the presence of intrinsic factor antibodies: Hashimoto’s thyroiditis, insulin dependent diabetes mellitus, Grave’s disease, rheumatoid arthritis, myasthenia gravis, hypoparathyroidism and Lambert-Eaton syndrome.
Less than 1.20 AU/mL: Negative
Results are considered negative for the detection of intrinsic factor antibody. Samples with ratios less than the negative cut-off are reported as negative.
1.21 to 1.52 AU/mL: Equivocal
Results that are above the negative cut-off and below the positive cut-off are regarded as equivocal and are reported as equivocal
Greater than 1.53 AU/mL: Positive
Results are considered positive for the detection of intrinsic factor antibody and are reported as positive
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