It is found most frequently in persons who are white and of European ancestry.  Frequency rates for this group have been cited at 1 in 500 to 1 in 700, depending on the source.  Therefore,  most research studies of IgA deficient persons have been done in persons of European descent.

IgA is deficient in these individuals because their B-lymphocytes, cells which normally produce IgA, are unable to mature into IgA-producing plasma cells.  IgA deficient persons appear to have IgA-bearing B-cells that are arrested at an immature stage of development.

The disorder is termed "selective" because other serum immunoglobulins, such as IgM and IgG, are present at normal or increased levels.  Additionally, IgA deficient persons have normal or near normal T-cell, phagocytic cell and complement system function

The IgA class of immunoglobulins has the specific function of protecting the body's mucosal surfaces (eyes, mouth, throat, lungs, gastrointestinal, and genitourinary tract) from infection.  While IgA is aided in this role to some degree by other classes of immunoglobulins, the lack or severe deficiency of IgA at these body sites makes one or more prone to recurrent infection, allergies, chronic diarrhea, or autoimmune diseases.  In autoimmune diseases, the immune system mistakenly attacks the body's own tissues.

Medical research has not yet determined the exact cause or causes of Selective IgA Deficiency.  In some families, there is evidence of familial occurrence, suggesting both autosomal dominant (only one abnormal gene is required which dominates the other) and recessive modes (two abnormal genes, one from each parent, are required) of transmission. Selective IgA Deficiency also occurs frequently in immediate relatives of persons with Common Variable Immunodeficiency, suggesting similarity in causes of the two disorders.

In rare cases, partial IgA deficiency has been linked to deletions of the IgA1 or IgA2 genes on chromosome 14, as well as to genes in the major histocompatibiilty complex on chromosome 6.  This region determines powerful antigens that produce strong T-cell responses.  Other reports link the disorder to partial deletion of the long or short arm of chromosome 18, which results in what is called the 18-q syndrome:  carp shaped mouth, reduced prominence of the mid facial area, nystagmus (involuntary, rapid, rhythmic eye movement, hypotonia (reduced muscle strength), atretic (congenital absence or closure), or stenotic (abnormal narrowing or constriction) ear canals, hearing loss, and mental retardation.  However, the vast majority of persons with Selective IgA Deficiency have evidence of chromosomal abnormalities.

The association of IgA deficiency has been found in some patients with ataxia-telegiectasia (irregularities or failure of muscle coordination affecting eyes and skin), frequent respiratory infections, and immunodeficiency (re:  Louis Bar Syndrome), a hereditary, progressive disease.

Thus, some IgA deficient persons may be totally unaware of their antibody deficiency with no more than the usual number of upper respiratory infections and/or occasional diarrhea.

 For those IgA deficient patients with a history of recurrent infections, the most common presentation is ear infections, sinusitis, and/or pneumonia  Other infection sites can be the throat, the gastrointestinal tract or the eyes.  These infections may become chronic and may not completely clear up with a course of antibiotics, necessitating prolonged antibiotic therapy.

Allergies are another common presentation of Selective IgA Deficiency, and also may be quite varied, ranging from mild to sever.  Common allergic reactions include asthma and food allergies.  Asthma in some IgA deficient patients may be severe and less responsive to drug therapy.  Food allergies may result in symptoms such as diarrhea or abdominal cramps.  A link between Selective IgA Deficiency and allergic rhinitis or eczema is uncertain.

Another, more unusual form of allergy that occurs in persons who have a total absence of IgA is an allergic reaction to IgA.  Exposure through blood products containing IgA causes some IgA deficient individuals to develop antibodies against this foreign protein.  In some cases, no previous exposure to blood or blood products is known but such an antibody appears anyway.  If an anti-IgA antibody develops, a massive  allergic reaction can result during blood or plasma transfusions.  If possible, IgA deficient persons who need blood should be tested for autoantibodies (antibodies to the body's own tissues) to IgA before receiving blood products containing IgA.  If autoantibodies exist, the IgA deficient person could receive washed red blood cells, or blood products from another blood type matched IgA deficient donor or from an autologous (from one's own body) blood donation.

The incidence of autoantibodies (antibodies to the body's own tissue) in IgA deficiency are believed to  be high, possibly as high as 40%.  These autoantibodies may be directed against IgG, smooth muscle, mitochondria (portion of a cell that is its energy source), basement membrane (thin layer under mucous membrane composed of collagen), desoxynucleoprotien (DNA)(portion of the cell that carries genetic information), thyroglobulin (protein from thyroid gland) and parietal cells (cells in the wall of the stomach).  However, the presence of such antibodies is not necessarily associated with disease.

Autoimmune diseases (immune system mistakenly attacks the body's own tissues) comprise the third common clinical presentation of persons with Selective IgA Deficiency.  Autoimmune diseases occur in Selective IgA Deficiency when patients produce antibodies to their own tissues, damaging some of their organs or tissues.  Autoimmune diseases most frequently associated with Selective IgA Deficiency include rheumatoid arthritis, systemic lupus erythematosus and Sjögren's Syndrome (a syndrome more common in women, characterized by decreased lacrimal and salivary gland secretion).  These diseases may present as sore and swollen joints of the hands or knees, a facial rash, anemia (decreased red blood cells or hemoglobin), or abnormally low platelet count.

Other autoimmune diseases associated with Selective IgA Deficiency affect the endocrine system, blood forming organs, or the gastrointestinal system.  These include thyroiditis (inflammation of the thyroid gland), hemolytic anemia (anemia caused by increased red blood cell destruction), and chronic active hepatitis (chronic inflammation of the liver).

Diseases and genetic disorders reported to be associated with Selective IgA Deficiency include:

• Allergic disorders
• Recurrent infections
• Asthma
• Food Allergies
• Crohn's Disease
• Relation  to patient with hypogammaglobulinemia
• Celiac disease  (an intestinal malabsorption syndrome characterized by diarrhea, malnutrition, and low calcium levels)
• Chromosomal abnormality
• Possible malignancy
• Endocrinopathy (any disease caused by disorder of the endocrine glands)
• Hyersplenism (an increased spleen activity causing anemia, increased red blood cell destruction, and spleen enlargement) and thrombocytopenia (abnormally low platelet count)
• Intestinal nodular hyperplasia (excessive formation of intestinal nodes)
• Recurrent giardiasis (protozoan infection)
• Pulmonary hemosiderosis (deposits of iron-containing pigment from hemoglobin in lungs due to red blood cell destruction)

Autoimmune diseases associated with Selective IgA Deficiency include:

Confirmation of Selective IgA Deficiency is made though a laboratory test which measures IgA levels in the blood or serum.  In the IgA-deficient patient, IgA levels will either be absent or below 7mg/dl, while other classes of immunoglobulin are normal.  In a small percentage of cases, perhaps 10%, an IgA-deficient patient may also be deficient in IgG2.  T-cells, phagocytic cells, and the complement system are normal or near normal.

Tests to further evaluate Selective IgA Deficiency include:

1.Tests to measure serum immunoglobulin concentrations,  These tests are performed by single radial diffusion, radioimmunoassay, ELISA, or automated laser nephelometry.

2.Assessment of IgG2.  These tests include radioimmunoassay, ELISA, or other methods of measuring this fraction.

3.Assessment of antibody formation following immunization.  These may include assessment of antigens or actual immunizations followed by such tests.  IgA-deficient persons usually have normal antibody response, but have a poor response to vaccines for certain bacterial pathogens.

4.Tests that measure circulating B- and T-lymphocytes.  These tests are usually not necessary.  However, if they are  employed, their purpose is to count B-lymphocytes by detection of membrane-bound immunoglobulin or monoclonal antibodies to B-cell antigens using immunofluorescence.  T-lymphocytes can be counted by immunofluorescence with monoclonal antibodies.

For example, steroids or immunosuppressive treatment may be needed in patients with systemic lupus erythematosus (chronic inflammation of connective tissue, affecting skin, joints, kidneys and the nervous system), autoimmune diseases (immune system mistakenly attacks body's own tissues), or antibiotics for infections.

Gammaglobulin treatment is not used in IgA Deficiency unless IgG2 Subclass Deficiency and/or antibody deficiency is also present.  Commercial gammaglobulin preparations do not contain much IgA, and even if IgA-rich preparations were produced, the infused IgA appears not to go to the mucous membranes where this protein is needed.  If anti-IgA antibodies are known to be present, IgA depleted intravenous immunoglobulin are available and safe (brand name:  Gammagard SD and Polygam SD).