Patients who have received a vitamin B12 injection within the last 2 weeks may have high serum vitamin B12 levels, which can interfere with this assay leading to false-positive results. All positive intrinsic factor blocking antibody (IFBA) results that have not been ordered through the ACASM / Pernicious Anemia Cascade reflex to vitamin B12 measurement. If this yields a level above 800 ng/L, a comment is appended to the report indicating a possible false-positive result.
Some patients with other autoimmune diseases may have positive IFBA assays without suffering from pernicious anemia (PA). This is reported particularly in patients with autoimmune thyroid disease or type I diabetes mellitus. In the validation of this assay, 24 individuals with these autoimmune endocrine diseases were tested and all were IFBA negative. However, 5 of 15 of patients with rheumatoid arthritis were IFBA positive during the validation of this assay. The literature suggests such individuals may, in fact, be at risk of later development of PA.
Since this is a competitive binding assay, the risk of heterophile antibody interference is low. During validation, 24 human antimouse antibody positive specimens and 25 specimens with other heterophile antibodies were tested and all were IFBA negative. However, if the clinical picture does not agree with the IFBA test result, the laboratory should be consulted for advice.
The cobalamins, also referred to as vitamin B12, are a group of closely related enzymatic cofactors involved in the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A and in the synthesis of methionine from homocysteine. Vitamin B12 deficiency can lead to megaloblastic anemia and neurological deficits. The latter may exist without anemia, or precede it. Adequate replacement therapy will generally improve or cure cobalamin deficiency. Unfortunately, many other conditions, which require different interventions, can mimic the symptoms and signs of vitamin B12 deficiency. Moreover, even when cobalamin deficiency has been established, clinical improvement may require different dosages or routes of vitamin B12 replacement, depending on the underlying cause. In particular, patients with pernicious anemia (PA), possibly the commonest type of cobalamin deficiency in developed countries, require either massive doses of oral vitamin B12 or parenteral replacement therapy. The reason is that in PA patients suffer from gastric mucosal atrophy, most likely caused by a destructive autoimmune process. This results in diminished or absent gastric acid, pepsin and intrinsic factor (IF) production. Gastric acid and pepsin are required for liberation of cobalamin from binding proteins, while IF binds the free vitamin B12, carries it to receptors on the ileal mucosa, and facilitates its absorption. Most PA patients have autoantibodies against gastric parietal cells or intrinsic factor, with the latter being very specific but only present in approximately 50% of cases. By contrast, parietal cell antibodies are found in approximately 90% of PA patients, but are also found in a significant proportion of patients with other autoimmune diseases, and in approximately 2.5% (4th decade of life) to approximately 10% (8th decade of life) of healthy individuals.