Castle factor, or intrinsic factor or IF factor, is a protein secreted by the parietal cells of the stomach and is essential for the absorption of vitamin B12 from food. What are the causes and symptoms of its deficiency? What is the anti-Castle factor antibody test? How to interpret the test results and what is its price?

Castle factor , or intrinsic factor (IF), is a glycoprotein secreted by the fundus parietal cells. Castle's Factor is responsible for the absorption of vitamin B12 from the diet. By creating a complex with vitamin B12, it protects it against digestive enzymes in the digestive tract.

Then, in the terminal ileum, the vitamin B12-Castle factor complex is absorbed after binding to specific receptors on the surface of the intestinal epithelial cells.

Castle factor (internal factor, IF) - causes of deficiency

Congenital Castle Factor Deficiency is a very rare disease caused by mutations in the GIF.webp gene that are inherited in an autosomal recessive manner. The first symptoms of congenital Castle factor deficiency appear very early (before the age of 5).

A more common cause of Castle factor deficiency is the autoimmune process by which the body produces antibodies to the factor.

The consequence of the autoimmune process is vitamin B12 deficiency and the appearance of Addison-Biermer disease (or pernicious anemia). Antibodies can block the binding of vitamin B12 to Castle factor or block the binding of vitamin B12-Castle factor complex to specific receptors.

This is a disease that results in the loss of parietal cells that produce the Castle Factor. The disease is progressive and begins with mild inflammation, where it results in a complete disappearance of the Castle factor and vitamin B12 deficiency over a period of several years.

The main symptom is megaloblastic anemia and neuropsychiatric disorders. Addison-Biermer disease is much more common in people from northern Europe than in people from other regions of Europe and Africa. In addition, the disease very often coexists with other diseases withauto-aggression.

Other causes of Castle factor deficiency include the condition after partial or complete gastrectomy and atrophic gastritis caused by Helicobacter pylori infection.

Castle factor (intrinsic factor, IF) - deficiency symptoms

The consequence of the Castle factor deficiency is the inability to absorb vitamin B12 and its deficiency. Vitamin B12 plays a key role in the formation of the hematopoietic system, myelin sheaths in neurons and the synthesis of neurotransmitters. Therefore, the symptoms of Castle factor deficiency include :

  • chronic fatigue
  • fatigue
  • pale skin and mucous membranes
  • depression
  • memory problems
  • headaches and dizziness
  • numbness and / or tingling in the extremities
  • sensory disturbance
  • visual acuity weakening

Castle factor (internal factor, IF) - indications for the test

  • differentiation of macrocytic anemia
  • low blood levels of vitamin B12
  • suspicion of Addison-Biermer disease
  • presence of autoimmune diseases such as type 1 diabetes, Addison's disease, Hashimoto's disease
  • atrophic gastritis

Castle factor (internal factor, IF) - what is the test?

Castle's factor can be determined in gastric juice collected with a tube after prior administration of pentagastrin (a synthetic form of gastrin).

Another approach is indirect diagnosis of Castle factor deficiency using the Schilling test. The test consists in swallowing a tablet containing radiolabelled vitamin B12 by the patient and administering unlabeled vitamin B12 intramuscularly after 1-2 hours.

The urine excretion of vitamin B12 is then measured 24 hours later. However, given the complexity of the test and the problems associated with the use of radioactive agents, the test is rarely used today.

The most common and, at the same time, the least invasive test is the determination of antibodies against Castle's factor in the blood, which are considered a specific marker of Addison-Biermer disease (they occur in 40-80% of patients). Anti Castle Factor antibodies are mainly IgG antibodies and come in two forms:

  • blocking the binding of vitamin B12 to the Castle factor
  • blocking the attachment of vitamin B12-Castle's factor complex to specific receptors on the surface of epithelial cells

Antibodies are present in both blood and gastric juice. However, the latter is dominated by IgA antibodies. Testis performed on an empty stomach from venous blood taken from the elbow bend. The price of the test is between PLN 70-120.

Laboratory methods used to determine antibodies to Castle's factor include Westernblot, ELISA and CLIA. They allow the detection of both forms of antibodies, using recombinant human antigens. In addition, CLIA and ELISA methods are characterized by high sensitivity and specificity and allow for the quantitative assessment of the level of antibodies, which is very helpful in monitoring the disease.

Castle Factor (Internal Factor, IF) - Results

The presence of anti-Castle factor antibodies with concomitant megaloblastic anemia, low vitamin B12 levels, positive Schilling test or atrophic gastritis indicates Addison-Biermer disease.

A negative result for anti-Castle factor antibodies does not always rule out Addison-Biermer disease, as half of the patients do not have these antibodies.

In case of doubt, it is worth considering additionally testing antibodies against parietal cells, which may also be present in people with Addison-Biermer disease.

References:

  1. Caquet R. 250 laboratory tests - when to commission, how to interpret. PZWL Publishing House Warsaw 2012, 2nd edition.
  2. Internal diseases, edited by Szczeklik A., Medycyna Praktyczna Kraków 2005.
  3. Bizzaro N. and Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014, 13 (4-5), 565-8.
About the authorKarolina Karabin, MD, PhD, molecular biologist, laboratory diagnostician, Cambridge Diagnostics Polska A biologist by profession, specializing in microbiology, and a laboratory diagnostician with over 10 years of experience in laboratory work. A graduate of the College of Molecular Medicine and a member of the Polish Society of Human Genetics. Head of research grants at the Laboratory of Molecular Diagnostics at the Department of Hematology, Oncology and Internal Diseases of the Medical University of Warsaw. She defended the title of doctor of medical sciences in the field of medical biology at the 1st Faculty of Medicine of the Medical University of Warsaw. Author of many scientific and popular science works in the field of laboratory diagnostics, molecular biology and nutrition. On a daily basis, as a specialist in the field of laboratory diagnostics, he runs the content department at Cambridge Diagnostics Polska and cooperates with a team of nutritionists at the CD Dietary Clinic. He shares his practical knowledge on diagnostics and diet therapy of diseases with specialists at conferences, training sessions, and in magazines and websites.She is particularly interested in the influence of modern lifestyle on molecular processes in the body.

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