How do I order Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM) tests for evaluating immunity?

How to Order IgG, IgA, and IgM Tests for Immunity Evaluation

To evaluate immunity through immunoglobulin testing, order serum IgG, IgA, and IgM levels as the first step, followed by specific antibody response testing if clinically indicated. 1, 2

Initial Laboratory Evaluation

• Order quantitative serum immunoglobulin levels (IgG, IgA, and IgM) as the first-line screening test for suspected antibody deficiency 2
• These tests measure the three major immunoglobulin classes that comprise approximately 80% (IgG), 15% (IgA), and 5% (IgM) of normal serum immunoglobulins 3
• Include a complete blood count (CBC) to evaluate for potential lymphopenia or other hematologic abnormalities that might suggest immune dysfunction 1
• If clinical suspicion remains high despite normal total immunoglobulin levels, consider ordering IgG subclass testing (IgG1, IgG2, IgG3, and IgG4) 4, 2

When to Order These Tests

• Order these tests for patients with recurrent sinopulmonary infections, particularly with encapsulated bacteria 1, 4
• Consider testing in patients with bronchiectasis, as immune deficiency occurs in approximately 5-6% of these cases 1
• Testing is indicated when evaluating for primary antibody deficiency syndromes including Common Variable Immune Deficiency (CVID) and Specific Antibody Deficiency (SAD) 1, 2
• Order these tests when infections are resistant to standard treatment or when there's a family history of immunodeficiency 1

Functional Antibody Response Testing

• After measuring baseline immunoglobulin levels, assess functional antibody responses by measuring specific antibody titers to both protein and polysaccharide antigens 1, 2
• For protein antigens, measure antibody responses to tetanus and diphtheria toxoids 1
• For polysaccharide antigens, measure pneumococcal antibodies before and after immunization with 23-valent pneumococcal polysaccharide vaccine 1
• Collect post-immunization samples 4-8 weeks after vaccination 1

Interpretation Guidelines

• Normal IgG subclass values are defined as within 2 standard deviations of the mean 1, 4
• For pneumococcal vaccine responses in adults, protective threshold is generally considered to be >1.3 μg/mL for more than 70% of serotypes tested 1, 2
• A polyclonal rise in serum IgG and IgA is commonly seen in patients with chronic infection and inflammation 1
• Abnormal IgG subclass levels should be confirmed with at least one additional measurement at least one month apart 1, 4

Common Pitfalls to Avoid

• Don't diagnose IgG subclass deficiency based on a single low measurement; confirm with repeat testing 1, 4
• IgG4 is present in very low concentrations in children younger than 10 years, so IgG4 deficiency should not be diagnosed before this age 1
• Be aware that some medications can cause secondary immunoglobulin deficiencies (antiepileptics, gold, penicillamine, hydroxychloroquine, NSAIDs) 1, 4
• Normal total IgG does not exclude subclass deficiency; conversely, isolated low subclass levels may not be clinically significant 4
• IgG replacement therapy should not be initiated based solely on laboratory values without clinical correlation 4

Additional Considerations

• If monoclonal immunoglobulin is detected, further investigation is needed to diagnose potential myeloma, Waldenstrom's macroglobulinemia, chronic lymphatic leukemia, or monoclonal gammopathy of uncertain significance (MGUS) 1
• Consider testing for autoimmune diseases in patients with IgA deficiency, as there is a higher prevalence of autoimmunity in these patients 5
• In patients with recurrent infections and normal immunoglobulin levels, consider Specific Antibody Deficiency (SAD) by evaluating vaccine responses 2
• Some patients with immunoglobulin deficiencies may develop into more severe phenotypes like CVID over time, requiring ongoing monitoring 4, 2