Celiac disease is diagnosed through a combination of blood tests and, in most cases, a small intestine biopsy. The process typically starts with a screening blood test that looks for specific antibodies your immune system produces in response to gluten, followed by an upper endoscopy to confirm the diagnosis by examining tissue samples from your small intestine.
The Initial Blood Test
The first step is a blood test measuring tissue transglutaminase IgA antibodies, commonly called tTG-IgA. This is the primary screening test because it’s both accurate and widely available, with a sensitivity of about 88% and specificity of 95%. A positive result doesn’t confirm celiac disease on its own, but it’s a strong signal that further testing is warranted. A negative result, on the other hand, is highly reliable at ruling out celiac disease in people with low to moderate risk.
There’s one important catch: about 2-3% of people with celiac disease also have IgA deficiency, a condition where the body doesn’t produce enough of the IgA antibody class. Since the standard screening test relies on IgA, these patients will get a falsely negative result. If your total IgA level is low, your doctor should order IgG-based versions of the test instead, such as IgG tissue transglutaminase or IgG deamidated gliadin peptide antibodies.
A second antibody test, called endomysial antibodies (EMA-IgA), is sometimes used alongside tTG-IgA. It’s slightly more specific at 97% but less sensitive at about 78%, so it’s better at confirming a positive result than catching every case.
You Must Be Eating Gluten for Tests to Work
This is the single most important thing to understand about celiac testing: both blood tests and biopsies require you to be actively eating gluten. If you’ve already gone gluten-free before getting tested, your antibody levels may have dropped and your intestinal lining may have started healing, leading to falsely normal results.
If you’ve already removed gluten from your diet and need accurate testing, a gluten challenge is necessary. Current recommendations suggest eating a minimum of 3 to 6 grams of gluten per day (roughly one to two slices of wheat bread) for at least 12 weeks before testing. If gluten causes only mild or no symptoms, eating up to 10 grams daily for longer is encouraged to increase confidence in the results. For people who develop severe symptoms, an abbreviated challenge of 6 to 12 weeks is considered acceptable, though it comes with a small risk of inconclusive results.
Confirming the Diagnosis With Biopsy
For most adults, a positive blood test leads to an upper endoscopy with duodenal biopsies. During this procedure, a thin flexible tube with a camera is passed through your mouth and into the upper part of your small intestine (the duodenum). Multiple tissue samples are taken, typically four to six from different sites, because celiac damage can be patchy rather than uniform.
A pathologist examines the samples for a pattern of damage characteristic of celiac disease. The changes are graded using a system called the Marsh classification. In early celiac disease (Marsh 1), the only visible change is an increase in certain immune cells within the intestinal lining. As the disease progresses, the tiny finger-like projections that line the intestine (villi) begin to flatten and the tissue architecture reorganizes (Marsh 3). This villous atrophy is the hallmark finding and the most definitive evidence of celiac disease on biopsy.
The American College of Gastroenterology recommends biopsy for confirmation in both children and adults. Even in patients with high clinical suspicion, biopsy provides the clearest diagnostic certainty and helps establish a baseline for monitoring healing later.
When Children Can Skip the Biopsy
One significant exception exists for pediatric patients. European guidelines from ESPGHAN allow a no-biopsy diagnosis in children when two specific conditions are met: the tTG-IgA level is at least 10 times the upper limit of normal, and a second, separate blood sample confirms positive endomysial antibodies. When both criteria are satisfied, the diagnosis is considered reliable enough to skip endoscopy.
Children with positive tTG-IgA at lower levels (below that 10-times threshold) still need biopsies to reduce the risk of a false positive diagnosis. The no-biopsy pathway is designed for clear-cut cases only, using tests that are calibrated specifically to measure these high values accurately.
The Role of Genetic Testing
Celiac disease is strongly linked to two genetic markers: HLA-DQ2 and HLA-DQ8. Nearly all people with celiac disease carry one or both of these gene variants. The combination test has a negative predictive value of over 99%, meaning that if you don’t carry either gene, celiac disease is essentially ruled out.
The flip side is that roughly 30-40% of the general population carries these genes without ever developing celiac disease, so a positive genetic test tells you very little on its own. Genetic testing is most useful in specific situations: screening family members of someone with celiac disease, resolving ambiguous blood test and biopsy results, or evaluating someone who went gluten-free before being properly tested.
When Blood Tests Are Negative but Suspicion Is High
A small percentage of people with celiac disease test negative on standard blood antibodies, a condition called seronegative celiac disease. Studies estimate this affects roughly 1 to 4% of all celiac patients. In one study of 312 confirmed celiac patients, about 4% were seronegative.
Because of this, the American College of Gastroenterology recommends that patients with a high pretest probability of celiac disease (persistent symptoms, a strong family history, or an associated autoimmune condition) should proceed to endoscopy with biopsy even if their blood tests come back negative. Relying on serology alone would miss these cases entirely.
Distinguishing Celiac From Gluten Sensitivity
Non-celiac gluten sensitivity (NCGS) can produce many of the same symptoms as celiac disease, including bloating, diarrhea, fatigue, and abdominal pain, but it is a separate condition. The key difference is that NCGS does not produce the characteristic celiac antibodies (tTG or EMA) and does not cause the villous atrophy seen on biopsy. On biopsy, people with NCGS typically show either completely normal tissue or only a mild increase in immune cells without structural damage.
There is currently no reliable blood test for NCGS. About half of patients test positive for a different, older antibody (IgG anti-gliadin), but this marker isn’t specific enough to be diagnostic. The current gold standard for diagnosing NCGS is a structured elimination and challenge protocol: first removing gluten and documenting symptom improvement, then reintroducing gluten (and a placebo) in a blinded fashion to confirm that gluten specifically triggers symptoms. In practice, this formal protocol is cumbersome, and many diagnoses are made through clinical observation and exclusion of celiac disease and other conditions.
When Symptoms Persist After Diagnosis
Most people with celiac disease improve on a strict gluten-free diet. When symptoms persist despite careful dietary adherence for 12 months or longer, doctors consider refractory celiac disease. This is rare and comes in two forms. Type 1 refractory celiac disease involves persistent intestinal damage with normal-appearing immune cells and generally responds to additional treatment. Type 2 involves abnormal, clonal immune cells in the intestinal lining and carries a more serious prognosis, including a risk of intestinal lymphoma. Distinguishing between the two types requires specialized laboratory testing on biopsy samples, including immunohistochemistry and molecular analysis to detect abnormal immune cell populations.