Anti–Intrinsic Factor Antibodies

Pernicious anaemia (PA) is characterised by chronic atrophic gastritis and reduced vitamin B12 intake in the ileum. Clinical features include megaloblastic anaemia and very often neurological conditions. PA is an autoimmune disease: its pathogenesis involves autoantibodies against Intrinsic Factor and gastric parietal cells. Cell-mediated immune mechanisms also play an important role.

The prevalence of anti–parietal cell antibodies decreases over the course of disease. Although these antibodies are highly sensitive (80–90%), their specificity is low because PA is associated with many other diseases (e.g., autoimmune thyroid disease, vitiligo, diabetes mellitus, Addison’s disease and others).

There are two types of autoantibody against Intrinsic Factor (IF):

• Blocking antibodies (type I) that inhibit the binding between vitamin B12 and Intrinsic Factor, preventing formation of the IF/vitamin B12 complex;
• Binding antibodies (type II) that recognise the Intrinsic Factor/vitamin B12 complex.

Anti-IF (type I) or anti-complex IF/B12 (type II) antibodies are determined using ELISA in both serum and gastric juice (where they are usually more frequently present); they are highly specific for PA and, if the patient presents megaloblastic anaemia, their presence makes the diagnosis virtually certain. Type 1 antibodies are present in 70% of patients, while type 2 antibodies are present in 35% of patients and only in combination with type 1 antibodies.