Celiac disease is an autoimmune disorder where consuming gluten, a protein found in wheat, barley, and rye, triggers an immune response. This reaction leads to inflammation and damage within the small intestine, impairing its ability to absorb nutrients. Blood tests are the most common initial step for screening this condition, detecting specific antibodies the body produces in response to gluten exposure. Understanding what these serology tests measure and how to interpret the results is necessary for an accurate diagnosis, though they do not constitute a final diagnosis on their own.
The Specific Antibody Tests Used
The primary screening tool for celiac disease involves a panel of blood tests designed to detect autoantibodies. The most sensitive and specific of these is the Tissue Transglutaminase IgA antibody (tTG-IgA) test, which targets an enzyme found throughout the body. This enzyme, tissue transglutaminase, is modified by the immune system in people with celiac disease, making it the central focus of the immune response.
Another important measure is the Endomysial Antibodies (EMA-IgA) test, which identifies antibodies that target the connective tissue surrounding smooth muscle fibers. While this test is highly specific, it is more labor-intensive and less commonly used than the tTG-IgA test. Both tTG-IgA and EMA-IgA are IgA-class antibodies, which are the most useful form because they are produced in the intestinal lining.
For some individuals, a test for Deamidated Gliadin Peptide (DGP) antibodies is also included, typically looking for both IgA and IgG classes. Gliadin is the component of gluten that triggers the immune response, and DGP is a modified form that the immune system specifically recognizes. The DGP-IgG test is particularly important for children under two years old and for patients who cannot produce enough IgA antibodies.
A crucial component of the testing panel is the measurement of Total Serum IgA, which determines the overall level of IgA in the blood. Since the primary celiac tests rely on IgA antibodies, a low total IgA level can lead to a false negative result, even if celiac disease is present. If an IgA deficiency is detected, the laboratory will often reflex to the IgG-based tests, such as tTG-IgG or DGP-IgG, to ensure an accurate screening.
Essential Preparation and Accuracy Factors
The accuracy of celiac disease blood tests is significantly dependent on the patient’s diet leading up to the blood draw. The body must be actively producing the antibodies for them to be detected, which requires continued consumption of gluten. This is known as the “gluten challenge,” and a patient must typically be eating gluten daily for at least several weeks before the test.
Starting a gluten-free diet before testing can cause the intestinal lining to heal and antibody levels to drop, potentially resulting in a false-negative serology test. If a patient is already following a gluten-free diet, a physician may recommend a monitored gluten challenge to reactivate the immune response before testing can proceed. The IgA deficiency is another factor that impacts accuracy, as it affects approximately two to three percent of people with celiac disease.
If the Total Serum IgA test reveals a deficiency, the IgA-based celiac tests will be unreliable. In these cases, IgG-based tests, such as DGP-IgG and tTG-IgG, become necessary, as these antibodies are not affected by an IgA deficiency and provide a reliable indicator of the autoimmune reaction.
Interpreting the Antibody Results
The laboratory report for a celiac disease blood test will typically provide a numerical value for each antibody measured, often compared to an upper limit of normal (ULN). A positive result indicates that the specific antibodies are present, suggesting an immune reaction to gluten has occurred. The higher the numerical value, or “titer,” the greater the probability that celiac disease is present.
Results are often categorized as negative, borderline, or positive. A Tissue Transglutaminase IgA (tTG-IgA) result that is ten times greater than the upper limit of normal (10x ULN) is considered a very high titer. This extremely elevated level is highly predictive of celiac disease, especially in children, and may allow for a diagnosis without an immediate intestinal biopsy in some European guidelines.
For adults, even a highly elevated titer, such as a tTG-IgA greater than 10x ULN with a positive Endomysial Antibody (EMA) test, still frequently requires a confirmatory biopsy. Borderline or weakly positive results are less conclusive and may be due to other factors or a very early stage of the disease. In these situations, a physician will almost always recommend a follow-up procedure to confirm the diagnosis.
A negative result on the antibody tests means that the specific celiac-related antibodies were not detected in the blood sample. This outcome makes celiac disease less likely, but it does not completely rule it out, especially if the patient was not consuming gluten before the test or has an IgA deficiency.
Beyond Serology: Confirmation and Monitoring
Once blood test results suggest a high probability of celiac disease, the next step in the diagnostic process is an intestinal biopsy. This procedure, performed during an upper endoscopy, is considered the gold standard for confirming the diagnosis. The doctor inserts a flexible tube with a camera down the throat to visually examine the small intestine and take tissue samples.
The tissue samples are then analyzed for the characteristic damage to the villi, the small, finger-like projections lining the small intestine. This visual and microscopic evidence of villous atrophy is what definitively confirms the presence of celiac disease.
Genetic testing for the HLA-DQ2 and HLA-DQ8 genes may be performed, but this test serves primarily as a tool to rule out celiac disease. Nearly all people with celiac disease carry one or both of these genes, but having the genes does not mean a person has the disease, only that they have the genetic predisposition. A negative genetic test, however, makes a diagnosis of celiac disease highly unlikely.
After a celiac disease diagnosis, the same antibody tests are used to monitor adherence to a strict gluten-free diet. Successful management of the condition should lead to a gradual reduction in antibody levels as the small intestine heals. Persistent elevation of tTG-IgA or EMA-IgA antibodies suggests that the patient may still be consuming gluten or that the intestinal healing is incomplete.