Tissue Transglutaminase IgA (tTG-IgA)

tTG-IgA (tissue transglutaminase IgA) is an antibody that people with celiac disease, an autoimmune reaction to gluten that damages the small intestine, make against an enzyme in their own gut lining. The American College of Gastroenterology (ACG) names it the preferred single blood test for celiac disease in people over age 2 ¹. A negative result is conditional, and a positive result is graded. A normal result makes celiac disease unlikely only if two things were true when your blood was drawn: you were eating gluten regularly, and your total IgA was normal. A positive result means more the further it sits above the lab's upper limit. Going gluten-free before the test lowers tTG-IgA, so a person with real celiac disease can get a normal result; this is why the test is ordered before any diet change.

tTG-IgA sits on both sides of that line. It is sensitive enough to be the first-line screen, so a valid negative carries weight, and at high multiples of the upper limit it is specific enough to act as a confirmer ¹. Low positives behave like neither, which is why they get a second test. The autoimmune antibodies explainer covers how screens and confirmers differ. If you also have an ANA, anti-CCP or anti-dsDNA result, those pages explain each one.

Why you must still be eating gluten

tTG-IgA is made only while gluten keeps triggering the immune reaction. When gluten leaves the diet, tTG-IgA falls over months and the gut lining starts to heal, so both the blood test and the biopsy can come back normal in someone who has celiac disease ¹. The ACG advises testing before gluten is removed and warns against starting a gluten-free diet on your own before testing ¹. Your clinician decides what 'eating gluten' means for your test, and some people who have already cut gluten are offered a supervised gluten challenge (a planned period of eating gluten again before re-testing).

If you are already gluten-free and do not want to re-introduce gluten, ask about HLA-DQ2 and HLA-DQ8 genetic testing. Almost everyone with celiac disease carries one of these two gene types, so a negative HLA result makes celiac disease very unlikely whatever you have been eating; a positive HLA result proves little, because these genes are common in people without celiac disease ¹.

Why total IgA is checked alongside tTG-IgA

tTG-IgA is an IgA antibody, so a person who makes little or no IgA cannot produce a positive result. Selective IgA deficiency is about 10 to 15 times more common in people with celiac disease than in the general population, affecting about 2 to 3% of them ¹². For that reason the ACG suggests measuring total IgA alongside tTG-IgA when celiac disease is strongly suspected or IgA deficiency is possible, and many labs run it routinely ¹. When total IgA is low, clinicians switch to IgG-based tests: deamidated gliadin peptide IgG (DGP-IgG) or tTG-IgG, celiac antibody tests of the IgG class that still work when IgA is low ¹². The total IgA page explains what IgA levels mean on their own.

There is no separate 'optimal' level for tTG-IgA. The target is below the lab's upper limit, and any value above it counts as positive. The raw number is less useful than its multiple of that limit: 30 U/mL can be barely positive on one kit and several times the limit on another ². The lab units explainer covers units in general terms.

What a weakly positive tTG-IgA means

A low-positive tTG-IgA (about 1 to 3 times the upper limit) is the least specific band. Low positives can show up in people with type 1 diabetes (blood sugar topic), autoimmune liver or thyroid disease (thyroid topic) and some infections without celiac damage in the gut, and they can also be the first sign of real celiac disease ¹. That is why low positives are usually followed by an endomysial antibody test (EMA-IgA, a more specific antibody test read under a microscope) or a biopsy before any change to the diet.

How celiac disease is confirmed

1. 1tTG-IgA plus total IgA, on glutenOne blood draw, no fasting needed. If total IgA is low, IgG-based tests (DGP-IgG or tTG-IgG) are added ¹.
2. 2Endomysial antibody (EMA-IgA) if neededUsed to firm up a low-positive tTG-IgA, and required on a second blood sample for the pediatric no-biopsy route ².
3. 3Upper endoscopy with small-bowel biopsy in adultsA gastroenterologist takes several small samples from the duodenum (the first part of the small intestine) to look for flattened villi, the finger-like folds that absorb food. This is the usual confirmation for adults with a positive tTG-IgA ¹.
4. 4No-biopsy route for some childrenESPGHAN allows diagnosis without biopsy when tTG-IgA is 10 or more times the upper limit and EMA-IgA is positive on a second sample ². The ACG notes this route may be considered in some adults, but biopsy remains standard ¹.

Celiac disease often shows up first on other lab results. Unexplained iron deficiency or anemia, B12 deficiency, low vitamin D, early osteoporosis and a mildly raised ALT on a liver enzyme panel are common reasons a clinician orders tTG-IgA ¹.

tTG-IgA after diagnosis tracks the diet

Once celiac disease is confirmed, tTG-IgA is repeated to check that gluten is staying out of the diet ¹. On a strict gluten-free diet the level usually falls; reaching normal often takes 6 to 24 months, sometimes longer. Many clinicians recheck it about 6 and 12 months after diagnosis and then once a year, so ask your clinician when your next draw should be. A level that stays high, or climbs after falling, usually points to hidden gluten exposure and is worth raising with your clinician or a dietitian.

This is one of the few autoantibody tests where repeating it and watching the trend is useful. The general case for trends is in why trends beat single readings.

Practicalities: ordering, cost and who should be screened

• Fasting: not needed. tTG-IgA and total IgA come from a routine blood draw.
• Ordering: tTG-IgA is a separate order from standard panels, and total IgA is a second line item. Many labs sell them together as a 'celiac panel'.
• Cost: insurance usually covers the test when there is a documented reason such as symptoms, anemia or a family history. If you are paying cash, ask the lab for a price before the draw.
• Medications: some immune-suppressing drugs, such as steroids, may lower the result, so tell your clinician what you take.

Celiac disease affects about 1.4% of people worldwide by blood test and about 0.7% by biopsy ³. In first-degree relatives (parents, siblings, children) of someone with celiac disease, a meta-analysis found a pooled prevalence of about 7.5% ⁴, and the ACG supports testing relatives who have symptoms or lab signs and considering it for those who do not ¹. People with type 1 diabetes, autoimmune thyroid disease, Down syndrome or Turner syndrome are also tested more often ¹.

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons.US Preventive Services Task Force, 2017 recommendation statement ⁵

The US Preventive Services Task Force made no recommendation for or against testing the general public, so tTG-IgA is ordered for symptoms, suggestive lab results or higher-risk groups. If you are in one of those groups and have never been tested, raise it with your clinician. More on gut-related markers is in the gut topic, and related immune tests are in the autoimmune topic.

Your results, in contextAdd the lab results you already have, and LifeFrom reads each marker next to the others it moves with, in plain language, with the sources it used.Get started