Explanation

Antibodies against intrinsic factor: what is measured?

Intrinsic factor is a protein from the stomach lining that binds vitamin B12 from food, so the small intestine can absorb it. In an autoimmune inflammation of the stomach lining (autoimmune or atrophic gastritis), the immune system makes antibodies against intrinsic factor or against the parietal cells that make it. As a result, too little B12 is absorbed and after years a deficiency can develop, which is called pernicious anemia. The test shows whether antibodies against intrinsic factor are present in the blood.

What can it detect?

Pernicious anemia: a vitamin B12 deficiency due to an autoimmune inflammation of the stomach lining
Autoimmune (atrophic) gastritis as the cause of a confirmed B12 deficiency

Result

What does the result mean?

Positive result

A positive result means that antibodies against intrinsic factor were found. They are not present in healthy people, and in someone with a B12 deficiency they make pernicious anemia or an autoimmune inflammation of the stomach lining very likely as the cause. The uptake of B12 through the stomach is then permanently disturbed, so treatment with B12 is usually needed for life. With a positive result without a B12 deficiency, the meaning is less clear, because the test has mainly been studied in people with a deficiency.

Negative result

A negative result means that no antibodies against intrinsic factor were found. That does not rule out pernicious anemia: according to the Dutch GP guideline (NHG) on anemia, the antibodies are present in only about half of people with atrophic gastritis, and according to the Dutch Society for Clinical Chemistry (NVKC) in about 80 in 100 people with pernicious anemia. A B12 deficiency can also have other causes, such as diet, a bowel disease, stomach or bowel surgery, or medicines.

After an abnormal result

With a positive result, the GP assumes pernicious anemia and treatment with vitamin B12 is usually lifelong, often starting with injections. Because other deficiencies and autoimmune diseases are also more common with an autoimmune inflammation of the stomach, the GP may for example check iron and thyroid function or refer you to a gastroenterologist for a stomach examination (gastroscopy).

Reliability

How reliable is the test?

The test is very specific: a positive result makes the diagnosis likely. The sensitivity is low, so a negative result does not rule out the condition; sometimes antibodies against parietal cells or gastrin are then measured. According to the Dutch GP guideline (NHG) on anemia, in a B12 deficiency without a known cause the result does not change the treatment (lifelong B12).

What can affect the result?

A B12 injection or a high dose of B12 shortly before the sample collection can give a false-positive result with some measuring methods.
A negative result does not rule out pernicious anemia.
There is no international standard for this test; results from different laboratories are not always comparable.

Who it is for

Who is the test useful for?

Useful for

Useful with a confirmed vitamin B12 deficiency without a clear cause, such as a vegan diet or stomach or bowel surgery, especially at an older age or with other autoimmune diseases, such as a thyroid disease or type 1 diabetes. Without a proven B12 deficiency, the meaning of a positive result is unclear, because the test has mainly been studied in people with a deficiency. Even with a B12 deficiency, the result usually does not change the treatment.

How common is it?

According to the Dutch GP guideline (NHG) on anemia, an autoimmune inflammation of the stomach lining is the most common cause of anemia due to a B12 deficiency; anemia due to a B12 or folic acid deficiency develops in general practice in about 2 in 1,000 people per year. Pernicious anemia mainly occurs at an older age. There is no Dutch figure for how often the antibodies occur in people without symptoms.

The Dutch GP guideline (NHG) on anemia and MDL Fonds

Drawbacks and risks

A negative result can give false reassurance: pernicious anemia remains possible and a proven B12 deficiency still needs to be treated.
A false-positive result shortly after a B12 injection can lead to a wrong diagnosis of a lifelong condition.

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