The most frequent cause of cobalamin malabsorption is pernicious anemia [14] in which the
atrophy of the gastric parietal cells results in a lack of secretion of both IF and chlorhydric acid. The
disease has an incidence of 25/100,000 and affects people aged 60 years or older, although in recent
years, there has been an increased number of patients younger than 60. Pernicious anemia is an
autoimmune disease sometimes associated with other autoimmune diseases, such as thyroiditis (both
Graves and Hashimoto diseases), Addison disease and vitiligo. In pernicious anemia, both anti-gastric
parietal cells (precisely, the anti-acid-producing enzyme, H+/K+ATPase) and anti-IF antibodies can be
found. There are two types of anti-IF antibodies. Type I antibodies are specific for the IF
cobalamin-binding site; type II antibodies bind to the cobalamin-IF complex, preventing its binding to
the specific ileal receptors. Some observations suggest that a different (perhaps cellular) autoimmune
mechanism may also be involved. Anti-IF antibodies are important clues to the diagnosis of pernicious
anemia, since such antibodies can be found in serum or gastric juice in approximately 60% and 75% of
patients with pernicious anemia, respectively. Without the presence of these antibodies, the diagnosis
relies on the Schilling test or on “ex juvantibus” criterion, i.e., cobalamin supplementation [1].