IgA Deficiency

At a Glance

Diagnosis of IgA deficiency should be considered in patients who have frequent and/or severe recurrent sinusitis, otitis, or pneumonia caused by typical encapsulated bacteria, such as streptococcus (including pneumococcal disease), staphylococcus, and hemophilus. Unexplained bronchiectasis, reflecting recurrent or persistent pneumonitis, should also raise the possibility of IgA deficiency.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The appropriate screening tests are measurement of total serum immunoglobulin IgA, IgG, and IgM concentrations. If the IgA concentration is low and IgG and IgM concentrations are normal (using appropriate age-adjusted reference ranges, since normal concentrations of immunoglobulins change from birth through young adulthood), selective IgA deficiency is likely. Testing should be repeated a few weeks to months later to confirm the values are persistently low. In addition, measurement of IgG subclass (IgG1, IgG2, IgG3, and IgG4) concentrations can be considered, since depression of one or more IgG subclass concentrations together with IgA deficiency increases the risk of recurrent infection.(Table 1)

Table 1.

Test Results Indicative of the Disorder
IgA concentration IgG concentration IgM concentration
8 mg/dL. (low) 800 mg/dL (normal) 100 mg/dL (normal)

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Age is an important determinant of normal immunoglobulin concentrations. Appropriate reference ranges in children should be used. Some infants have a transiently low concentration of immunoglobulins, which can resolve spontaneously as the child grows.

IgA and other immunoglobulin deficiencies may be secondary to other conditions, including protein-losing conditions and problems with low production.

Protein-losing conditions include nephrotic syndrome and protein-losing enteropathy. If immunoglobulin deficiency is due to protein loss, the serum albumin and total protein concentrations are also low.

Problems with low production exist. Synthesis of IgA and other immunoglobulins can be suppressed in association with multiple myeloma or after treatment with a variety of immunosuppressive or bone marrow-suppressing chemotherapies. Malnutrition, particularly protein-calorie malnutrition, may be associated with IgA and other immunoglobulin deficiency.

Selective IgA deficiency, the most common of the immunoglobulin deficiencies, is characterized by low concentrations of serum IgA and normal or near-normal concentrations of the other immunoglobulin classes (total IgG and IgM). If the other immunoglobulin classes are also low, a more complex immunodeficiency syndrome, such as common variable immunodeficiency or X-linked agammaglobulinemia in a boy, is likely present.

What Lab Results Are Absolutely Confirmatory?

Demonstration of repeatedly low IgA serum concentrations with normal concentrations of IgG and IgM confirms diagnosis.

Additional Issues of Clinical Importance

Failure to identify and treat IgA deficiency could lead to recurrent sinopulmonary infections with the potential for life-threatening or organ-damaging infection that might be prevented with gamma globulin infusions or prophylactic antibiotics. Patients with IgA deficiency should be given age-appropriate immunizations, so protective IgG and IgM antibodies are present.

Patients with total IgA deficiency may make antibodies that react with normal IgA, and presence of those antibodies could lead to anaphylaxis or anaphylactoid reactions or other potentially serious reactions during or after administration of normal blood-derived products containing IgA. Patients with recurrent infection and IgA deficiency may be treated with gamma globulin replacement, such as intravenous or subcutaneous infusions of gamma globulin, or may be administered blood or plasma products for other reasons. Those patients should be monitored closely for anaphylaxis during administration of gamma globulin or other blood products.

Serum tests can be performed to identify antibodies to IgA in the serum of patients with IgA deficiency, and presence of those antibodies is a significant risk factor for developing reactions to IgA-containing products. Fortunately, complete IgA deficiency (associated with anti-IgA antibodies) is uncommon, whereas partial IgA deficiency is relatively common.

Patients with congenital or acquired deficiencies in some complement components (e.g., complement C3 and C5) can have recurrent infections in a pattern very similar to those with immunoglobulin deficiencies. Measuring total hemolytic complement activity, which assesses the entire classical complement cascade, can be helpful to evaluate for possible complement deficiencies.

Some patients may have deficiencies in their ability to produce functional antibodies, even though total immunoglobulin concentrations are normal. This can be evaluated by testing levels of antibodies to specific antigens after immunization (e.g., antibodies to tetanus or pneumococcal antigens). It is important to note that patients with suspected immunodeficiencies can be immunized with inactivated microbes or isolated antigens but should not be immunized with live microbes because of the risk of significant infection.

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