Celiac disease is a chronic autoimmune condition that primarily targets the small intestine in genetically susceptible individuals. When people with this condition consume gluten (a protein found in wheat, rye, and barley), their immune system mistakenly mounts an attack. This defensive reaction involves producing specific antibodies, which act as markers of ongoing immune activity. Measuring these antibodies in the bloodstream offers a non-invasive way to screen for the disease and track its activity.
The Immune Response Triggered by Gluten
The immune cascade begins when gluten is broken down into gliadin peptides. These peptides cross the intestinal lining and enter the underlying tissue in genetically susceptible people (those with HLA-DQ2 or HLA-DQ8 genes). Once in the tissue, the enzyme tissue transglutaminase (tTG) modifies the gliadin peptides through deamidation.
The modified gliadin peptides are presented to specialized immune cells, triggering an adaptive immune response and antibody generation. The immune system also produces autoantibodies that target the tTG enzyme itself. This continuous immune attack causes inflammation and progressive damage to the villi, the small projections in the small intestine responsible for nutrient absorption.
Primary Antibodies Used for Celiac Screening
Diagnosis focuses on detecting three main types of autoantibodies produced by the immune response. The most common first-line test measures IgA antibodies against Tissue Transglutaminase (tTG-IgA), the enzyme mistakenly targeted by the immune system. The tTG-IgA test is highly sensitive and specific for celiac disease in most adults and older children.
A second test, the Endomysial Antibody (EMA), also detects antibodies directed against tTG. The EMA test is known for its high specificity and is often used as a confirmatory marker, though it is technically demanding. The third category measures antibodies against Deamidated Gliadin Peptides (DGP), the modified gluten fragments that initially trigger the immune reaction. DGP antibodies are measured in both IgA and IgG classes and are useful in specific patient groups.
Understanding Antibody Test Results
For antibody tests to be accurate, the patient must be consuming gluten regularly, a process called a “gluten challenge.” If a person has already started a gluten-free diet before testing, the immune reaction may subside, potentially leading to a false-negative result. A positive result, especially a high-titer result, strongly suggests the presence of active celiac disease.
The IgA class of antibodies, used in the primary tTG-IgA test, is absent in about two to three percent of the general population, a condition known as selective IgA deficiency. Celiac disease patients have a higher rate of this deficiency, meaning a standard tTG-IgA test could incorrectly return a negative result. Therefore, a total serum IgA level is often measured simultaneously to check for this deficiency.
If an IgA deficiency is confirmed, doctors rely on IgG-based antibody tests, such as Deamidated Gliadin Peptide IgG (DGP-IgG) or Tissue Transglutaminase IgG (tTG-IgG). These IgG antibodies can accurately detect the autoimmune response even when IgA is lacking. A negative result on all celiac-specific antibody tests, provided the patient was consuming gluten and is not IgA deficient, makes a diagnosis of celiac disease unlikely.
Monitoring Disease Activity After Diagnosis
Once a celiac disease diagnosis is confirmed (typically through a small intestinal biopsy), antibody tests shift from a diagnostic tool to a monitoring instrument. The only accepted treatment is a strict, lifelong gluten-free diet (GFD). Antibody levels are used to assess the body’s response to this dietary change, as adherence to the GFD stops the trigger and allows the inflammatory process to resolve.
As the small intestine heals and inflammation decreases, the levels of circulating autoantibodies, particularly tTG-IgA, are expected to drop over time. This reduction demonstrates that the immune system is calming down and that mucosal healing is likely occurring. Antibody levels should normalize within 12 months to two years of starting the GFD, though the timeline varies. Persistent elevation of celiac-specific antibodies after this period often indicates ongoing, possibly unintentional, gluten exposure or poor adherence to the diet.