Celiac Disease (CD) is an autoimmune disorder triggered by consuming gluten, a protein found in wheat, barley, and rye. In individuals with CD, gluten ingestion prompts an immune response that damages the lining of the small intestine. Immunoglobulin A (IgA) is an antibody class that plays a prominent role in this reaction and is generally used as a primary marker for diagnosis. The question of whether a low level of IgA indicates CD involves a complex interplay between immune function and diagnostic procedures. An underlying condition causing low total IgA introduces significant complications into the standard screening process.
The Role of Immunoglobulin A in Celiac Screening
Immunoglobulin A is the primary antibody class found in the body’s mucosal linings, including the gastrointestinal tract. This antibody acts as a first line of defense against ingested pathogens and foreign substances. In Celiac Disease, the immune system produces specific IgA antibodies that target the body’s own tissues in response to gluten exposure.
The standard initial screen for Celiac Disease measures the concentration of these disease-specific IgA antibodies in the blood. The most widely used test detects antibodies against tissue transglutaminase (tTG-IgA), an enzyme involved in the autoimmune damage seen in the small intestine. A highly elevated tTG-IgA level strongly indicates Celiac Disease in a patient consuming gluten. Because of its high sensitivity and specificity, the tTG-IgA test is the preferred first-line serological test for most patients.
Selective IgA Deficiency and Test Reliability
The reliability of the standard tTG-IgA test depends on a patient’s ability to produce sufficient IgA antibodies. Selective IgA Deficiency (SIgAD) occurs when a person produces very low or undetectable levels of IgA in the blood and mucosal secretions. SIgAD is the most common primary immunodeficiency worldwide, affecting about 1 in 500 people.
The prevalence of SIgAD is significantly higher among Celiac Disease patients, occurring in 2% to 3% of individuals with the condition. If a patient has both SIgAD and Celiac Disease, the standard tTG-IgA assay may return a negative result because the body cannot produce the necessary IgA antibodies. This low IgA level creates a diagnostic challenge, potentially masking the underlying Celiac Disease.
Current medical guidelines recommend performing a total serum IgA level test alongside the tTG-IgA test for every patient screened for Celiac Disease. If the total IgA level is low, the standard IgA-based antibody test is unreliable for that individual. The low IgA level flags the need for an alternative diagnostic approach to accurately determine if Celiac Disease is present.
Alternative Diagnostic Pathways When IgA is Low
When a low total IgA level is detected, diagnostic efforts pivot to antibody tests utilizing Immunoglobulin G (IgG). The immune system produces IgG antibodies in abundance, and their levels are unaffected by SIgAD. Therefore, IgG-based tests are used as substitutes to detect the autoimmune response in IgA-deficient patients.
The primary alternative tests measure anti-tissue transglutaminase IgG (tTG-IgG) and anti-deamidated gliadin peptide IgG (DGP-IgG). The DGP-IgG test is often preferred because it targets a modified component of gluten and provides a more reliable indicator of active disease than tTG-IgG alone in IgA-deficient individuals. Although IgG-based tests are generally less sensitive than IgA counterparts, they are necessary serological tools when IgA levels are compromised.
Genetic testing for the presence of the HLA-DQ2 and HLA-DQ8 genes also plays a significant role. Nearly all people with Celiac Disease possess at least one of these two human leukocyte antigen (HLA) haplotypes. Genetic testing cannot confirm a diagnosis but can effectively rule it out; if a patient lacks both HLA-DQ2 and HLA-DQ8, Celiac Disease is highly unlikely. Ultimately, a small intestine biopsy remains the definitive method to confirm Celiac Disease by visually confirming the characteristic damage.
The Underlying Relationship Between Low IgA and Celiac Disease
Low IgA levels do not directly cause Celiac Disease, but the two conditions are frequently found together due to a shared genetic predisposition. The strong association between SIgAD and Celiac Disease suggests a common underlying vulnerability in the immune system. SIgAD is linked to an increased risk of developing various autoimmune disorders, including Celiac Disease.
Research indicates that both SIgAD and Celiac Disease are associated with specific human leukocyte antigen (HLA) haplotypes, particularly the HLA-DQB102 allelic variants. These genes are necessary for the development of Celiac Disease in the vast majority of cases. The presence of these shared genetic factors may predispose an individual to both insufficient IgA production and a heightened autoimmune response to gluten.