Intrinsic factor antibodies are proteins produced by the immune system that are associated with pernicious anemia. This test detects intrinsic factor antibody (IF antibody) circulating in blood.
Intrinsic factor is a protein produced by a type of specialized cells that line the stomach wall known as parietal cells. During digestion, stomach acids release vitamin B12 from food and bind to intrinsic factor to form a complex. The formation of this complex is necessary for the absorption of vitamin B12 in the small intestine.
Among having functional roles in the brain and nervous system, vitamin B12 is important in the production of red blood cells. Without sufficient intrinsic factor, vitamin B12 goes largely unabsorbed and the body cannot produce enough normal red blood cells, leading to anemia. Besides anemia, decrease in the numbers of neutrophils and platelets may also occur.
Anemia that is due to a lack of intrinsic factor is called pernicious anemia. This is primarily an autoimmune condition that occurs when the body’s immune system targets its own tissues and develops antibodies directed against the parietal cells and/or the intrinsic factor. These antibodies can damage the parietal cells and disrupt intrinsic factor production or prevent intrinsic factor from carrying out its biological function.
The results of intrinsic factor antibody tests are often taken into consideration with the results of other laboratory tests to help make a diagnosis. When a person has a decreased vitamin B12 level and/or increased methylmalonic acid and homocysteine levels and has intrinsic factor antibodies, then it is likely that the person has pernicious anemia.
A negative test result does not necessarily mean that a person does not have pernicious anemia. As many as half of those affected will not have IF antibodies. When they are not present, the health practitioner may order a parietal cell antibody test to help establish the diagnosis. Parietal cell antibodies are not as specific as intrinsic factor antibodies. They are present in about 90% of those with pernicious anemia but may also be present in a variety of other conditions and in up to 10% of the general population.
Some people with autoimmune diseases such as type 1 diabetes, Hashimoto thyroiditis, Addison disease or Graves disease may have intrinsic factor antibodies without having pernicious anemia. The intrinsic factor antibody test is not used to diagnose or monitor these conditions.
Vitamin B12-associated anemia may take several years to develop as a normal person typically has large stores of B12 in reserve. Symptoms tend to emerge only when these stores become depleted.
References:
Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014 Apr-May;13(4-5):565-8. doi: 10.1016/j.autrev.2014.01.042. Epub 2014 Jan 11. PMID: 24424200. [L]
Ankar A, Kumar A. Vitamin B12 Deficiency. [Updated 2022 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing 2022 Jan-. [L]
Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med. 1997 Nov 13;337(20):1441-8. doi: 10.1056/NEJM199711133372007. PMID: 9358143. [L]
Osborne D, Sobczynska-Malefora A. Autoimmune mechanisms in pernicious anaemia & thyroid disease. Autoimmun Rev. 2015 Sep.14(9):763-8. doi: 10.1016/j.autrev.2015.04.011. Epub 2015 May 1. PMID: 25936607. [L]
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