Intrinsic Factor Blocking Antibody

Intrinsic factor is a protein that is produced by the parietal cells of the stomach. It binds to vitamin B12, thereby allowing absorption of the vitamin by intestinal cells. In pernicious anemia, an autoimmune disorder, autoantibodies are formed against intrinsic factor leading to its deficiency. The lack of intrinsic factor then causes malabsorption of vitamin B12 and subsequent anemia. Autoantibodies can also be formed directly against the parietal cells which similarly leads to inadequate intrinsic factor activity and vitamin B12 deficiency.

A positive IFAB test result indicates the presence of circulating autoantibodies to intrinsic factor. The combination of megaloblastic anemia, low serum vitamin B12, and the presence of serum IFAB strongly supports the diagnosis of pernicious anemia. Positive IFAB test results are also observed in some patients with other autoimmune disorders such as autoimmune thyroid disease and rheumatoid arthritis. These patients may be at risk for developing pernicious anemia at a later date.

The IFAB test is a competitive binding immunoassay employing an antibody that is specific to the B12 binding site on intrinsic factor. A high vitamin B12 concentration in the patient’s serum may interfere with the assay and cause a false-positive result. Thus, a patient receiving a vitamin B12 injection 1 to 2 weeks prior to testing may have a false-positive IFAB result. Conversely, a patient with a previously negative IFAB result may have a positive result on a subsequent test if the 2nd sample was collected within 1 to 2 weeks of a vitamin B12 injection. Therefore, we recommend waiting at least 1 week after vitamin B12 injection to collect samples for IFAB testing.

In pernicious anemia, patients may have several antibodies present, each playing a role in the etiology of the disorder. These include autoantibodies to intrinsic factor and to gastric parietal cells. Gastric parietal cell antibodies have a high sensitivity (around 85%) for pernicious anemia. Specificity is relatively low though, because antibodies can be found in up to 10% of healthy individuals and in other disorders, including other autoimmune disorders. In contrast, IFAB has a much lower sensitivity (about 50%), suggesting that a negative result does not rule out pernicious anemia. IFAB specificity is very high, which means that a positive IFAB confirms a pernicious anemia diagnosis.¹