Celiac disease testing typically starts with a simple blood draw that looks for specific antibodies your immune system produces in response to gluten. If that blood test comes back positive, the next step is usually a biopsy of your small intestine to confirm the diagnosis. The process is straightforward, but there are a few important details that can make or break the accuracy of your results.
The Blood Test That Starts the Process
The first test your doctor will order is a blood test that measures antibodies called tissue transglutaminase IgA (tTG-IgA). When someone with celiac disease eats gluten, their immune system produces these antibodies, which attack the lining of the small intestine. The tTG-IgA test catches roughly 90% to 95% of celiac cases, making it the preferred screening tool.
Your doctor will also check your total IgA level at the same time. About 2% to 3% of people with celiac disease have a condition called IgA deficiency, meaning their bodies don’t produce enough of this particular type of antibody. That’s ten times the rate in the general population. If your IgA is too low, the standard test won’t work properly, so the lab will automatically switch to a different antibody test that uses IgG instead. This backup test looks for antibodies against a specific fragment of gluten called deamidated gliadin peptide.
You Must Be Eating Gluten for Tests to Work
This is the single most important thing to know before getting tested: you need to be actively eating gluten. If you’ve already cut gluten out of your diet, your antibody levels will drop and your intestinal lining may start to heal, which can cause both blood tests and biopsies to come back falsely negative.
If you’ve already gone gluten-free, your doctor may ask you to do what’s called a gluten challenge. Current clinical guidance recommends eating 3 to 6 grams of gluten per day for at least 12 weeks before testing. That’s roughly one to two slices of wheat bread daily for three months. It can be uncomfortable if gluten genuinely makes you sick, but it’s the only way to get reliable results. Your doctor will typically check your baseline antibody levels before the challenge begins, then retest after the 12-week period.
Confirming the Diagnosis With a Biopsy
A positive blood test is a strong signal, but for most adults, the definitive diagnosis comes from an upper endoscopy with biopsies of the small intestine. During this procedure, a gastroenterologist passes a thin, flexible tube with a camera down your throat and into the first section of your small intestine, called the duodenum. The whole thing takes about 30 to 60 minutes, and you’re sedated for it, so you won’t feel anything. Afterward, you’ll stay at the clinic until you’re alert enough to leave safely.
During the endoscopy, the doctor collects tiny tissue samples. Current recommendations call for at least six biopsies taken from several different spots in the duodenum, because celiac damage can be patchy. A pathologist then examines those samples under a microscope and grades the damage using something called the Marsh classification. At the lower end (Marsh I), there’s an increase in certain immune cells in the intestinal lining but the finger-like projections called villi are still intact. At the more advanced stage (Marsh III), those villi are flattened or destroyed, which is what interferes with nutrient absorption and causes many of the symptoms people associate with celiac disease. Even people with early-stage changes (Marsh I or II) often improve significantly on a gluten-free diet.
When Children Can Skip the Biopsy
For children, European guidelines now allow a diagnosis without a biopsy in specific circumstances. If a child’s tTG-IgA level is at least 10 times the upper limit of normal on an accurate, calibrated test, and a second blood sample confirms the presence of a different celiac antibody called endomysial antibody (EMA-IgA), the diagnosis can be made without an endoscopy. This no-biopsy approach has been validated as safe and reliable in pediatric patients. It spares kids the sedation and procedure when the blood work is overwhelmingly clear. Adults with very high antibody levels are increasingly being diagnosed this way too, though biopsy remains the standard recommendation for most adult patients.
Genetic Testing: Useful for Ruling It Out
Genetic testing for celiac disease works differently from most diagnostic tests. It looks for two gene variants, HLA-DQ2 and HLA-DQ8, that are essentially required for celiac disease to develop. The test has poor positive predictive value, meaning that carrying these genes doesn’t mean you have or will get celiac disease (roughly 30% to 40% of the general population carries them). But it has very high negative predictive value: if you don’t carry either gene, celiac disease is virtually ruled out.
This makes genetic testing most useful in two situations. First, if you’ve already been on a gluten-free diet and don’t want to do a 12-week gluten challenge, a negative genetic test can practically eliminate celiac from consideration. Second, if your blood tests or biopsy results are ambiguous, genetic testing can help clarify whether celiac disease is even possible.
When Blood Tests Miss It
A small percentage of people with celiac disease, roughly 2% to 6%, are what doctors call seronegative, meaning their antibody blood tests come back normal despite having intestinal damage from gluten. If your blood tests are negative but your doctor still strongly suspects celiac disease based on your symptoms, the next step is typically an endoscopy with biopsy to look directly at the intestinal tissue.
Diagnosing seronegative celiac disease requires meeting several criteria: the biopsy shows villous atrophy, total IgA levels are normal (ruling out IgA deficiency as the reason for the negative blood test), and genetic testing confirms the presence of HLA-DQ2 or DQ8. Other conditions that can flatten the villi need to be excluded first. The diagnosis is then confirmed if symptoms and intestinal damage improve after 12 to 24 months on a gluten-free diet. It’s uncommon, but worth knowing about if your symptoms are persistent and unexplained.
What About Home Testing Kits?
Over-the-counter celiac test kits use a finger-prick blood sample to detect tTG antibodies, similar to the lab-based blood test. In professional settings, these rapid tests perform reasonably well, but when used on the general population, sensitivity has dropped to around 78% in studies. That means roughly one in five people with celiac disease could get a false negative from a home kit.
If you use a home test and it comes back positive, you still need a full lab-based blood test and, if that’s also positive, an endoscopy to confirm the diagnosis. A negative home test isn’t reliable enough to rule celiac disease out. These kits are best thought of as a nudge to pursue formal testing, not a substitute for it. Blood testing in general is also less reliable in children under 3, and a negative result at any age doesn’t guarantee you won’t develop celiac disease later.
Follow-Up Testing After Diagnosis
Once you’re diagnosed and start a gluten-free diet, testing doesn’t stop. Guidelines recommend follow-up visits every 3 to 6 months during the first year, then every 1 to 2 years after that. Each visit typically includes a dietary review, a repeat tTG-IgA blood test, and basic lab work to check for nutritional deficiencies.
Antibody levels are expected to fall on a strict gluten-free diet, but there’s an important nuance: normal antibody levels don’t necessarily mean your intestinal lining has fully healed. On the flip side, if your antibodies are still elevated 12 months after starting the diet, that’s a strong sign that gluten is still getting into your diet somewhere, whether intentionally or through cross-contamination. Some doctors will recommend a follow-up biopsy after one to two years to directly assess how well the intestine has recovered.