Clinical Information

Immunoglobulin A (IgA), the predominant immunoglobulin secreted at mucosal surfaces and the second most abundant immunoglobulin in serum, consists of 2 subclasses, IgA1 and IgA2. These subclasses differ in their molecular structure and tissue distribution. IgA1 is the major (approximately 80%) subclass in serum. It has a longer hinge region making it more susceptible to proteolytic cleavage. IgA2 is the major subclass in secretions such as milk, tears, sweat, and saliva. Although IgA deficiency is a common defect (1 in 700), it is usually asymptomatic. IgA deficiency with or without IgG subclass deficiency, however, can lead to recurrent pulmonary and gastrointestinal infections. In selective IgA deficiency, both IgA1 and IgA2 are deficient. It is also possible that only one of the subclasses is deficient. Some infections (eg, recurrent sinopulmonary infections with Haemophilus influenzae) may be related to a deficiency of IgA2, even in the presence of normal total IgA concentrations.

Paradoxically, bacterial infections may also cause IgA deficiency. IgA2 is more resistant to bacterial destruction than IgA1. Certain bacteria can cleave and inactivate IgA1, but not IgA2, thus depleting most of the IgA. In the presence of a concurrent IgA2 deficiency, infection by these organisms results in an apparent IgA deficiency.

IgA deficiency is a cause of anaphylactic transfusion reactions. In these situations, patients who are IgA deficient produce anti-IgA antibodies that react with IgA present in the transfusion product. While transfusion reactions typically occur in patients who have no detectable concentrations of IgA, they can also occur in patients with measurable IgA. In these situations, the complete deficiency of 1 of the IgA subclasses may be the cause of the transfusion reactions.