What is the role of lab tests in the workup of immunoglobulin A deficiency (IgAD)?

Updated: May 15, 2018
  • Author: Marina Y Dolina, MD; Chief Editor: Michael A Kaliner, MD  more...
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  • Immunoglobulin A deficiency (IgAD) is defined as an undetectable serum IgA level. In the past, this was usually confirmed with the low-level radial immunodiffusion method (lower limit of detection is 50 mg/mL [5 mg/dL]). However, this test is rarely done in current practice, and results are usually reported as < 0.07 g/L or < 0.05 g/L. The lower limit of detection differs depending on the sensitivity of the method used. It is usually 0.05-0.1 g/L for nephelometry, 0.05 g/L (5 mg/dL) for low-level radial immunodiffusion plates, and 0.0016 g/L for hemaglutination inhibition techniques. [76]

  • Almost all patients with IgAD also exhibit loss of both secretory IgA type 1 and secretory IgA type 2 in their external secretions, but these are not routinely measured.

  • Low serum IgA levels in children aged 6 months to 4 years should be confirmed to be persistently low at age 4 years before making a lifetime diagnosis of IgAD. Some children with a low level when aged 6 months to 4 years progress to common variable immunodeficiency (CVID), whereas others completely normalize.

  • Normal serum levels of IgG and IgM are necessary for a diagnosis of selective immunoglobulin A deficiency (SIgAD). Other causes of hypogammaglobulinemia and use of medications that reduce IgA levels should be excluded (see Differentials). A total IgG level within the normal range does not exclude specific IgG antibody deficiency (eg, deficient antibodies to polysaccharides), and this should be specifically sought in patients who have recurrent infections, total IgG levels toward the lower bound of normal, and IgA deficiency. Tests showing low IgA serum values in children younger than 5 years should be repeated. Some children with low levels progress to CVID, but levels can normalize by age 4-5 years.

  • The most common mistake clinicians make with this diagnosis is incorrectly diagnosing IgAD or transient hypogammaglobulinemia of infancy in children because they inappropriately use the adult reference range for serum IgA levels.

  • In an emergency setting, where transfusion reactions need to be interpreted quickly, gel immunoassays findings were compared with the results of fluorescence enzyme immunoassay. The gel screening assays did not quantify the level of anti-IgA antibodies, but they did provide an effective method for diagnosing anti-IgA-related anaphylaxis. [77]

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