What Does an IgA Test Assess?
An IgA test measures the level of Immunoglobulin A antibodies in your blood, which are the most abundant antibodies in the human body and serve as the primary defense system at mucosal surfaces—particularly in the respiratory and gastrointestinal tracts. 1, 2
Primary Functions of IgA
IgA performs several critical roles in immune defense:
Mucosal immunity: IgA is the dominant immunoglobulin in secretions that line the respiratory tract, gastrointestinal tract, and other mucosal surfaces, forming the first line of defense against pathogens attempting to breach these barriers. 3
Immune exclusion: Secretory IgA prevents pathogenic microorganisms from adhering to and penetrating mucosal surfaces, effectively blocking infection before it can establish. 4, 3
Maintenance of intestinal homeostasis: A large portion of gut microbiota is coated with IgA, which helps regulate the balance between beneficial commensals and potentially harmful pathobionts. 2, 4
Anti-inflammatory regulation: In the circulation, monomeric IgA that has not engaged antigen plays a role in dampening inflammatory responses. 2
Clinical Significance of IgA Testing
Detection of IgA Deficiency
Selective IgA deficiency is defined as IgA levels below 7 mg/dL (or 0.07 g/L) after age 4 years, with normal IgG and IgM levels—making it the most common primary immunodeficiency in humans. 5, 1
The prevalence varies dramatically by ethnicity: approximately 1 in 300-700 white individuals in the United States versus only 1 in 18,000 in Asian populations. 5
Most IgA-deficient individuals (approximately two-thirds) have detectable but very low IgA levels; only one-third have completely absent IgA. 5
Associated Clinical Conditions
When IgA deficiency is symptomatic, patients may present with:
- Recurrent infections of the respiratory and gastrointestinal tracts 5, 4
- Autoimmune diseases (IgA deficiency has significant associations with autoimmunity, suggesting common genetic linkages) 5, 1
- Celiac disease (occurs in 1.7-2.3% of celiac patients versus 0.1-0.3% of the general population) 6
- Allergic disorders and atopy 5, 4
- Malignancy (increased risk in some cases) 5, 1
Critical Diagnostic Implications
For Celiac Disease Testing
IgA deficiency renders standard IgA-based celiac serology falsely negative, potentially missing celiac disease diagnosis in affected patients. 5, 6
When total IgA is low or absent during celiac testing, IgG-based tests (particularly IgG deamidated gliadin peptide) must be ordered immediately instead. 6, 7
Approximately 2% of celiac disease patients are IgA deficient, which is 10-20 times higher than the general population. 5
For Other Serologic Testing
Many antibody-based diagnostic tests rely on IgA measurement (such as anti-tissue transglutaminase IgA, endomysial antibody IgA), so knowing the total IgA level is essential to interpret these results correctly. 5
If IgA is deficient, alternative IgG-based testing strategies must be employed to avoid false-negative results. 5, 6
Medication-Induced IgA Deficiency
IgA deficiency can be acquired through certain medications, and this is often reversible with drug cessation:
- Phenytoin, carbamazepine, valproic acid, zonisamide 5
- Sulfasalazine, gold, penicillamine 5
- Hydroxychloroquine and nonsteroidal anti-inflammatory drugs (NSAIDs) 5
A thorough medication history is essential when evaluating patients with low IgA levels. 5
Transfusion Considerations
Patients with IgA deficiency may develop antibodies to IgA, creating a theoretical risk for anaphylactic reactions to blood products (red cells, platelets). 5
Although the individual risk is likely small, some centers transfuse products from IgA-deficient donors or wash cells before transfusion for IgA-deficient recipients. 5
Genetic and Immunologic Context
IgA deficiency involves a maturation defect in B cells that prevents normal IgA production. 4
Certain MHC haplotypes (particularly the 8.1 haplotype) are significantly associated with both IgA deficiency and autoimmunity. 1
IgA deficiency and common variable immunodeficiency (CVID) likely exist on the same disease spectrum, with some IgA-deficient patients progressing to CVID over time. 5, 4