IgA deficiency is the most common primary immunodeficiency, with an occurrence ranging from 1/400 to 2,000 individuals. The frequency of IgA deficiency is greater in people of European descent and may be as high as 1 in 500. In the United States, whites are affected more than blacks by a ratio of 20:1. Asian Americans have an even lower incidence, with the occurrence in Japanese descendents being 1 in 18,500 persons.

IgA deficiency may be primary or secondary (acquired), sporadic, or familial. Both serum and secretory IgA are lacking in most patients and, rarely, one or the other is lacking. Inheritance is either autosomal recessive or dominant. The primary defect in selective IgA deficiency is related to a failure of B cells to differentiate in response to appropriate stimuli to mature isotype-switched surface IgA-positive B cells and IgA-secreting plasma cells. The basis for the defect is not known. Certain drugs, such as phenytoin, D-penicillamine, sulfasalazine, and hydroxychloroquine, have been associated with this entity. Congenital cases of noninherited IgA deficiency in association with rubella, cytomegalovirus, and Toxoplasma gondii have been reported.

Although some studies have reported recurrent infections in as many as 50% of IgA-deficient patients, most of these individuals are healthy. Some patients develop symptoms after an uneventful childhood and early adulthood. Recurrent or chronic upper and lower respiratory tract infections result in bronchiectasis or cor pulmonale in insufficiently treated patients. Gastrointestinal infection with Giardia lamblia infection is common as are a spruelike syndrome, ulcerative colitis, and Crohn disease.