Diagnostic Testing for Selective IgA Deficiency

Measure serum IgA level below 7 mg/dL (or age-specific lower limit) with normal IgG and IgM levels to diagnose Selective IgA Deficiency. 1

Primary Diagnostic Tests

Serum immunoglobulin levels are the cornerstone of diagnosis, measuring IgG, IgA, and IgM concentrations 1
IgA must be below 7 mg/dL (or below the age-dependent reference range) while IgG and IgM remain within normal limits to confirm selective IgA deficiency 1, 2, 3
Total serum protein and albumin levels should be measured to exclude secondary hypogammaglobulinemia from protein loss (nephrotic syndrome, protein-losing enteropathy), which would present with low albumin alongside low immunoglobulins 1, 2

Total B-cell count by flow cytometry helps distinguish selective IgA deficiency from more severe antibody deficiencies 1
B-cell numbers are typically normal in selective IgA deficiency, differentiating it from agammaglobulinemia where B cells are absent or severely reduced 1, 2

Specific antibody titers to protein antigens (diphtheria, tetanus, pertussis, conjugated pneumococcal or Haemophilus influenzae vaccines) should be measured 1
Antibody response to polysaccharide antigens using the 23-valent pneumococcal polysaccharide vaccine is essential to identify coexisting specific antibody deficiency 1
Measure pre-immunization and post-immunization titers (4-8 weeks after vaccination) to assess functional antibody production 1, 2

IgG subclass levels (IgG1, IgG2, IgG3, IgG4) should be measured, as 4% of patients with IgA deficiency have concurrent IgG subclass deficiency 1, 4
This is particularly important when patients have recurrent sinopulmonary infections despite normal total IgG levels 1, 4

Review medication history for drugs causing secondary IgA deficiency (anti-epileptics, certain antibiotics, gold) 2, 5
Evaluate for hematologic malignancies (B-cell lymphomas, multiple myeloma) that can cause secondary hypogammaglobulinemia 2
Assess for protein-losing conditions: check 24-hour urine protein or urine protein/creatinine ratio for nephrotic syndrome, and stool alpha-1 antitrypsin clearance for protein-losing enteropathy 2

Celiac disease screening with tissue transglutaminase (tTG) IgA is unreliable in IgA deficiency; use IgG-based tests (IgG-tTG or IgG deamidated gliadin peptide) instead 1, 6
Total IgA level measurement is critical before interpreting celiac serology, as 2-2.6% of celiac patients have IgA deficiency compared to 0.2% of the general population 1, 3
Consider screening for thyroid function (autoimmune thyroid disease), fasting glucose or HbA1c (type 1 diabetes), and other autoimmune markers given the high association 6, 4, 7

Complete blood count with differential to evaluate for cytopenias or lymphoproliferation 1
T-cell enumeration (CD4, CD8, NK cells) by flow cytometry if there are opportunistic infections suggesting combined immunodeficiency 1, 2
Genetic testing (microarray for copy number variation, targeted gene sequencing) may be considered in familial cases or when progression to common variable immunodeficiency is suspected 1

Never rely solely on IgA-based serologic tests (such as IgA-tTG for celiac disease) in patients with suspected or confirmed IgA deficiency, as these will be falsely negative 1, 6
Distinguish selective IgA deficiency from early common variable immunodeficiency (CVID) by confirming normal IgG and IgM levels; patients may progress from selective IgA deficiency to CVID over time, requiring ongoing monitoring 1, 2, 5
Document functional antibody deficiency through vaccine response testing rather than relying on immunoglobulin levels alone, as some patients have adequate antibody function despite low IgA 1, 4
Check for anti-IgA IgE antibodies in patients with complete IgA deficiency (<5 mg/dL) before administering blood products, as these patients are at risk for anaphylaxis with IgA-containing transfusions 5

Serial immunoglobulin measurements every 6-12 months to detect progression to more severe antibody deficiencies 4, 5
Reassess specific antibody responses if recurrent infections develop despite initially adequate vaccine responses 1, 4
Monitor for development of autoimmune complications (thyroiditis, celiac disease, arthritis, cytopenias) which occur in 11.5-18% of pediatric patients 4, 7