What additional laboratory tests are recommended for a patient with Selective IgA (Immunoglobulin A) Deficiency?

Additional Laboratory Testing for Selective IgA Deficiency

The most critical additional tests are functional antibody assessments (pre- and post-vaccination titers to protein and polysaccharide antigens), celiac disease screening with IgG-based tissue transglutaminase antibodies, and anti-IgA antibody testing to assess transfusion reaction risk. 1

Functional Antibody Assessment (Essential)

Your patient has normal IgG and IgM levels, but this does not guarantee functional antibody production. Measure specific antibody titers to protein antigens (diphtheria, tetanus, pertussis, conjugated pneumococcal or Haemophilus influenzae vaccines) to assess whether the patient can mount protective responses. 1

Antibody response to polysaccharide antigens using the 23-valent pneumococcal polysaccharide vaccine is essential to identify coexisting specific antibody deficiency, which occurs in a subset of IgA-deficient patients and significantly impacts clinical management. 1 Measure both pre-immunization and post-immunization titers (4-8 weeks after vaccination) to properly assess functional antibody production. 1

• Approximately 4% of patients with selective IgA deficiency will have confirmed deficiency in antibody production despite normal immunoglobulin levels. 2
• This functional assessment determines whether the patient requires more aggressive infection prophylaxis or even immunoglobulin replacement therapy in rare cases. 3

Celiac Disease Screening (Critical)

Screen for celiac disease using IgG-based tissue transglutaminase (tTG-IgG) antibodies, NOT IgA-based tests. 1 This is non-negotiable because:

• IgA deficiency occurs in 2-2.6% of celiac patients compared to 0.2% of the general population, making the association 10-fold higher. 3, 1
• IgA-based celiac serology (IgA-tTG, IgA-EMA) will be falsely negative in IgA-deficient patients. 3, 1
• Alternatively, use IgG-deamidated gliadin peptide (IgG-DGP) antibodies, which are suitable for IgA-deficient patients. 3

If celiac serology is positive or clinical suspicion remains high despite negative serology, proceed directly to duodenal biopsy. 3

Anti-IgA Antibody Testing (Essential for Safety)

Test for anti-IgA antibodies to assess risk of anaphylactic transfusion reactions. 1 This is critical because:

• Approximately 76.3% of IgA-deficient patients develop anti-IgA antibodies. 4
• These antibodies can cause severe, potentially fatal anaphylactic reactions during blood transfusions or intravenous immunoglobulin (IVIG) administration. 3, 5, 6
• The frequency of IgA deficiency with class-specific anti-IgA in blood donors is approximately 1 in 1,200. 4

If anti-IgA antibodies are present, the patient must receive only washed red blood cells, IgA-deficient blood products, or frozen deglycerolized red cells for any future transfusions. 5 IVIG is contraindicated in patients with anti-IgA antibodies due to anaphylaxis risk. 3

Protein and Albumin Measurement

Measure total serum protein and albumin levels to exclude secondary hypogammaglobulinemia from protein loss (nephrotic syndrome, protein-losing enteropathy), which would present with low albumin alongside low immunoglobulins. 1 This distinguishes primary from secondary immunodeficiency.

Monitoring for Progression to CVID

Repeat immunoglobulin levels (IgG, IgA, IgM) periodically because some patients with selective IgA deficiency will evolve to common variable immunodeficiency (CVID) over time. 1, 7

• Familial clustering occurs in 20-25% of cases, with family members having either selective IgA deficiency or CVID, suggesting shared genetic susceptibility. 7
• The distinction between selective IgA deficiency and early CVID requires confirming normal IgG and IgM levels; ongoing monitoring is essential. 1

Additional Testing Based on Clinical Context

Given the markedly elevated IgE (1,500 IU/mL) in your patient, consider:

• Specific IgE testing for common allergens to evaluate the atopic component, as 18.78% of IgA-deficient patients have atopic disease. 2
• Aspergillus-specific IgE if there are respiratory symptoms suggesting allergic bronchopulmonary aspergillosis (ABPA). 3

Complete blood count with differential to evaluate for cytopenias or lymphoproliferation, as autoimmune manifestations occur in 11.5% of IgA-deficient patients. 1, 2

Critical Pitfalls to Avoid

• Never rely on IgA-based serologic tests (IgA-tTG, IgA-EMA, IgA-endomysial antibodies) in this patient—they will be falsely negative. 3, 1
• Do not assume normal IgG/IgM levels mean normal antibody function—functional testing with vaccine responses is mandatory. 1
• Document anti-IgA antibody status prominently in the medical record and alert the blood bank to prevent potentially fatal transfusion reactions. 5, 4
• Distinguish selective IgA deficiency from partial IgA deficiency (IgA 7-70 mg/dL), which does not meet diagnostic criteria and has different clinical implications. 1, 7