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When blood tests results are highly positive, a biopsy might not be needed to diagnose celiac disease

June 26, 2024

Mildly elevated results not enough to get an accurate diagnosis for children or adults, studies suggest

By Amy Ratner, director of scientific affairs

Currently in the United States, children and adults usually need to have a positive celiac disease blood test, followed by an endoscopy and biopsy to definitively diagnose celiac disease. But scientists have been discussing whether celiac disease blood tests alone could be used for diagnosis, particularly in children.

This question was the basis of two studies presented as posters recently at Digestive Disease Week (DDW).

In one study researchers from 11 children’s medical centers in the United State and Canada set out to measure how accurate a blood test is in predicting who has celiac disease, called the positive predictive value. The second study, by researchers from six medical centers in the United States, similarly evaluated the blood test in adults.

In both studies, the tissue transglutaminase IGA (TTG-IgA) test was found to be accurate in predicting celiac disease in patients who had very high levels of TTG-IgA antibodies. However, the accuracy of the tests fell when predicting celiac disease in those whose blood tests were positive but not at extreme levels.


Highly positive blood tests results, 10 times the upper limit of normal, correctly predicted when children had celiac disease nearly 96 percent of the time, a study presented by M. Camilla Cardenas, MD, of the Mayo Clinic, found. But more than 4 percent of children with these results did not have celiac disease.

Of about 1,600 children in the study who had high levels of TTG-IgA, about 1,500 had the intestinal damage found in a biopsy that confirms a celiac disease diagnosis.  Another 73 children did not.

In the United States, guidelines from the North American Society for Pediatric Gastroenterology, Hepatology & Nutrition (NASPGHAN) call for both positive TTG-IgA tests and a biopsy showing damage to the intestine for celiac disease confirmation. Adult gastroenterological associations also recommend blood tests and a biopsy but allow in some cases for a diagnosis based on elevated levels of TTG-IgA and a positive endomysial antibody test.

European pediatric guidelines allow for a celiac disease diagnosis without a biopsy for children who meet certain criteria, including blood tests results 10 times the upper limit of normal. This has raised the question of whether the same no-biopsy approach could be used more routinely in the United States, particularly because an endoscopy with a biopsy is an invasive procedure.

During an endoscopy, a very thin, flexible tube is snaked from the mouth to the small intestine, and a small tool is used to take tissue samples, called biopsies, from the wall of the intestine. Patients are sedated, with the type and amount of sedation dependent on age and any other co-existing medical conditions.

The study also evaluated the accuracy of TTG-IgA test when all positive blood tests, not just highly positive tests, were considered.

Of about 3,800 children with any level of positive TTG-IgA, about 83 percent were confirmed to have celiac disease based on biopsy results.

Varying accuracy of TTG-IgA tests

The study’s evaluation of how well TTG-IGA tests work in positively predicting celiac disease in children found variation between tests made by different companies. That variation could lead to different results based on which test a child is given.

In children who had follow-up biopsies to confirm celiac disease, a test made by Thermo Fisher had the highest positive predictive value in both those who had a highly positive TTG-IgA result and those who had a TTG-IgA positive result. About 97 percent of children with high positive results had confirmed celiac disease and about 89 percent of those who had any positive result did as well.

This compared to results ranging from 95 percent to 90 percent in highly positive children and 81 to 76 percent in children with any positive result when tests made by Bio Rad and Inova were used.

This creates a need for standardization of tests or specific thresholds for each test if diagnosis was to be based on blood test results alone in the United States, the study concludes.


In the study that compared blood test and biopsy results, nearly 99 percent of adults who had ten times the upper limit of normal TTG-IgA were confirmed to have celiac disease. Of the 132 patients in this category, only two did not show a level of intestinal damage that indicated celiac disease.

The study included about 4,300 patients who were having an endoscopy and biopsy, with a TTG-IgA test before or shortly after the procedure. About 25 percent had some level of a positive TTG-IgA result. Overall, the positive predictive value of TTG-IgA was about 88 percent, the study presented by Claire Jansson-Knodell, MD, of the Cleveland Clinic, found.

On the flip side, when the TTG-IgA test was normal, the probability that a person did not have celiac disease was high, with a negative predictive value of about 93 percent.

“A noninvasive diagnosis of celiac disease may be accurate in selected American adults with high TTG-IgA, but caution is needed with a mildly elevated TTG-IGA-IgA,” the study concluded. In those with a mildly elevated TTG-IgA a biopsy may still be needed to confirm a celiac disease diagnosed, the study says.

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Studies presented at DDW are sometimes preliminary and give an early look at investigations that are likely to include more details as they progress toward publication in a peer reviewed scientific journal. Studies selected to be presented at DDW go through a review process.


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