Celiac disease is a chronic autoimmune disorder that primarily affects the small intestine, triggered by consuming gluten, a protein found in wheat, barley, and rye. When a genetically predisposed person ingests gluten, their immune system mistakenly launches an attack against their own tissues. This reaction involves the production of specific autoantibodies. Immunoglobulin A (IgA) is a major class of antibody that protects mucosal surfaces, such as the lining of the gut. Testing for these IgA-based antibodies in the blood is the standard first step in screening for celiac disease.
Standard Blood Testing for Celiac Disease
For most people with normal immune function, the diagnostic screening begins with a blood test that looks for the tissue transglutaminase IgA (tTG-IgA) antibody. The tTG-IgA test is widely preferred because it has high sensitivity and specificity for detecting celiac disease activity when a person is actively consuming gluten. This test measures the body’s immune response to the enzyme tissue transglutaminase, which is a target of the autoimmune reaction in celiac disease. Another IgA-based marker, the Endomysial Antibody IgA (EMA-IgA), is often used to confirm a positive tTG-IgA result because it is highly specific. All celiac blood tests require the individual to be on a gluten-containing diet to ensure antibody production.
Understanding Selective IgA Deficiency
Selective IgA Deficiency (SIgAD) is a distinct immunological condition where an individual produces low or undetectable levels of IgA antibodies, while the levels of other antibodies, such as Immunoglobulin G (IgG) and Immunoglobulin M (IgM), remain normal. SIgAD is recognized as the most common primary immunodeficiency, affecting approximately one in every 500 people. Many people with SIgAD experience no symptoms, but for others, it can lead to a higher risk of recurrent infections and autoimmune disorders. This condition has a significant association with celiac disease, as people with SIgAD are estimated to be 10 to 20 times more likely to develop celiac disease compared to the general population. Because the standard screening tests for celiac disease rely on IgA antibodies, the presence of SIgAD means a person with active celiac disease may not produce enough IgA antibodies for the standard test to register as positive.
Diagnosing Celiac Disease When IgA Is Low
A low IgA level does not automatically mean a person has celiac disease, but it does mean the standard IgA-based tests will be unreliable and may produce a false negative result. Therefore, the first step is to measure Total Serum IgA to confirm the presence of an IgA deficiency. If the total IgA level is confirmed to be low or absent, the clinician must pivot to a specialized diagnostic protocol to accurately screen for celiac disease. This shift is designed to prevent a missed diagnosis that can occur when the body cannot produce the necessary IgA antibodies. The alternative protocol focuses on looking for celiac-specific antibodies that belong to the IgG class.
IgG-Based Testing
The two primary IgG-based tests used are the Tissue Transglutaminase IgG (tTG-IgG) and the Deamidated Gliadin Peptide IgG (DGP-IgG) antibodies. These tests are used because individuals with SIgAD generally have a normal ability to produce IgG antibodies, allowing the immune system to mount a detectable response to gluten in this different antibody class. A positive result on either of these IgG tests indicates that the person is likely producing an autoimmune response to gluten. The DGP-IgG test is particularly valued in cases of IgA deficiency due to its high sensitivity in detecting celiac disease activity. While these IgG-based tests are less specific for celiac disease than their IgA counterparts in the general population, a positive result from the IgG panel necessitates the next diagnostic step when IgA levels are low.
Confirmation and Management After Testing
Even with positive IgG blood test results in the setting of low IgA, the diagnosis of celiac disease is not yet definitive. The gold standard for confirmation remains an upper endoscopy with small intestinal biopsy, during which a gastroenterologist takes tissue samples for analysis. The pathologist examines the tissue for signs of inflammation and damage, such as villous atrophy—the flattening of the villi. This damage is classified using the Marsh criteria, where a finding of Marsh stage 3 is considered diagnostic of active celiac disease. A positive biopsy, combined with positive serology and clinical symptoms, establishes the diagnosis, requiring lifelong management via a strict, gluten-free diet (GFD).