Celiac disease is an autoimmune disorder where consuming gluten, a protein found in wheat, barley, and rye, triggers an immune response that damages the small intestine. This reaction involves the body mistakenly attacking its own tissue. When Celiac disease is suspected, the initial diagnostic step is a blood screening test, known as serology, which looks for specific immune markers. While designed as a highly accurate screening tool, the test’s accuracy is not absolute and depends heavily on several biological and behavioral factors.
Understanding Celiac Disease Blood Screening
Celiac disease blood screening detects elevated levels of autoantibodies produced by the immune system in response to gluten exposure. The two primary antibodies measured are Immunoglobulin A (IgA) class of anti-Tissue Transglutaminase (tTG-IgA) and Endomysial Antibodies (EMA-IgA).
The tTG-IgA test is the first-line screening tool due to its high reliability and cost-effectiveness. It measures antibodies targeting the tissue transglutaminase enzyme. The EMA-IgA test has high specificity but is often reserved for confirmation because it is technically more demanding and expensive.
For patients with a compromised immune system or IgA deficiency, doctors use tests for Deamidated Gliadin Peptides (DGP). DGP tests measure both IgA and Immunoglobulin G (IgG) antibodies, targeting modified gluten proteins. These are useful when standard IgA-based tests are unreliable.
Key Factors That Impact Test Accuracy
Celiac disease serology is generally reliable; the tTG-IgA test often shows sensitivity above 90% and specificity over 95% in adults. Sensitivity is the ability to correctly identify those with the disease, while specificity identifies those without it. However, several patient-specific conditions can compromise these high accuracy rates.
The most common factor affecting accuracy is the patient’s gluten consumption, known as the “gluten challenge.” The body must be actively exposed to gluten to produce antibodies. A patient already on a gluten-free diet may produce an insufficient antibody response, resulting in a false-negative test. For reliable results, guidelines suggest consuming gluten at least once a day for several weeks before the blood test.
A pre-existing IgA deficiency also compromises IgA-based tests. This condition, more common in Celiac patients, prevents the production of sufficient IgA antibodies. If only the standard tTG-IgA test is performed, the result will be falsely negative despite active intestinal damage. To counteract this, total serum IgA levels are measured alongside tTG-IgA. If a deficiency is identified, the physician switches to IgG-based tests, such as DGP-IgG or tTG-IgG.
Age plays a role, particularly in children under two years old, where the tTG-IgA test can be less accurate because their immune systems are not fully matured. For this age group, the Deamidated Gliadin Peptide (DGP) IgA and IgG tests are often recommended as the initial screening tool.
Confirmation and Exclusions: Beyond the Blood Test
A positive blood test is highly suggestive but is not a definitive diagnosis. The conclusive step for adults remains an upper endoscopy with a small bowel biopsy. The biopsy allows a physician to physically examine and analyze the small intestine tissue for characteristic damage caused by the autoimmune reaction.
This damage appears as villous atrophy, which is the flattening of the villi responsible for nutrient absorption. Pathologists use scoring systems to grade the severity of this damage, confirming the presence of an immune-mediated enteropathy. The biopsy provides the histological proof necessary for a permanent diagnosis, especially when serology results are ambiguous.
Genetic testing for Human Leukocyte Antigens (HLA) serves primarily as an exclusionary tool. Nearly all people with Celiac disease carry one or both specific genetic markers: HLA-DQ2 or HLA-DQ8. Since these genes are also present in a large portion of the healthy population, a positive result does not confirm the disease. However, a negative result, where neither gene is present, effectively rules out Celiac disease with high certainty. This testing is valuable when blood tests are negative but suspicion remains high, or when a patient has already begun a gluten-free diet.