Biopsies and Gene Tests Play a Role in Celiac Disease Diagnosis

August 23, 2016

Biopsies and Gene Tests Play a Role in Celiac Disease Diagnosis


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Some gaps in knowledge about still exist (part two of a two-part story)

Test Tubes

(Part two of a two-part story)

By Amy Ratner, Beyond Celiac Medical and Science News Analyst

A variety of tests are used to diagnose someone with celiac disease. The Agency for Healthcare Research and Quality (AHRQ), which works within the U.S. department of Health and Human Services, recently evaluated the pool of scientific evidence related to blood and gene tests and biopsies and video capsule endoscopy to determine how accurate these methods of diagnosis are.

The path to diagnosis can vary depending on a patient’s age, family history of celiac disease and other health conditions. Generally, blood tests (see part one) are followed by a biopsy. Gene testing can also be part of the process.

The study review looked at the sensitivity and specificity of the blood and gene tests and the effectiveness and risks of the biopsy and video capsule endoscopy.

Although the agency concluded tests commonly used in the US are effective, it also noted that there are some significant gaps in knowledge about celiac disease diagnosis.

Gene Testing

Testing for genes commonly found in those who have celiac disease, HLA-DQ2 and HLA-DQ8, was found to have “excellent sensitivity and negative predictive value.” This makes the test useful for ruling out celiac disease, but not diagnosing it, the review noted. Genetic tests are recommended as a step in the diagnostic process by the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and American College of Gastroenterology (ACG).

Diagnosis of celiac disease can begin with gene testing, but because the test can only rule out and not confirm a diagnosis, blood testing is often the first step, followed by endoscopy with biopsy.

Genetic tests are seen as most helpful for children because a negative result settles the question of whether of child in a family with celiac disease will ever develop it. “Genetic testing is a popular option for young children with a family history of celiac disease, because it can be done via a cheek swab, so no needles, and if it is negative, the child does not need to be tested periodically for celiac disease via blood testing,” said Benjamin Lebwohl, MD, assistant professor of clinical medicine and epidemiology at

In adults, the genetic test is helpful when someone with a family history of celiac disease has already started a gluten-free diet or when the antibody blood tests and biopsy give conflicting results, according to Ciaran Kelly, MD, medical director of the Celiac Center at Beth Israel Deaconess Medical Center and Beyond Celiac scientific/medical advisory council member.

The Biopsy

A biopsy that shows signs of damage to the intestine, called villous atrophy, followed by recovery on a gluten-free diet is the internationally accepted gold standard for celiac disease diagnosis, the study review noted.

Risk from a biopsy was found to be very low despite patient concern about perforations, bleeding, pain and discomfort. But the review study noted the accuracy of the biopsy can depend on where it is done, with some evidence that celiac disease is under diagnosed by pathologists in community settings compared to those in academic medical facilities. Additionally, the review found strong evidence that multiple biopsy specimens should be taken for accurate results.

The hallmark of recovery on the diet also seems to be more elusive than once thought. “Recent studies from a variety of countries and practice settings have found that a substantial minority of patients with celiac disease do not heal on repeat biopsy,” Dr. Lebwohl said. It’s not always clear why a patient does not heal or has incomplete healing. In some cases, healing just takes longer, but in others the cause is ongoing low-level gluten exposure, he noted.

Some patients are reluctant to have a biopsy, preferring video capsule endoscopy. For this test, adult patients swallow a capsule containing a tiny camera which takes pictures to determine if the intestinal damage that marks celiac disease is present. The study review found that the video capsule is “safe and fairly accurate,” but there is some risk of retaining the capsule. And most blood tests have a higher sensitivity and specificity than this procedure, the study noted.

Peter Green, MD, president of the North American Society for the Study of Celiac Disease (NASSCD) said he was surprised by the study review’s findings on video capsule endoscopy. “To my mind it does not have any role in the regular diagnosis of celiac disease,” he said, noting that video capsule endoscopy is used infrequently and mainly in unusual cases. “If the biopsy is the gold standard, the video capsule endoscopy is not a biopsy.”

ESPGHAN guidelines allow diagnosis of celiac disease without a biopsy if a patient has tTG test results that are 10 times the normal limit, positive gene and EMA testing and responds to a gluten-free diet. These guidelines have not been accepted in the US. The study review found evidence to support this kind of multiple-testing strategy without a biopsy, but noted that additional studies are needed.


Several gaps in knowledge about celiac disease diagnosis and areas where evidence is lacking were noted in the study review. It is difficult to compare the way various methods of diagnosis have impacted clinical decisions, patients’ adherence to the gluten-free diet, their quality of life and symptoms because few studies have evaluated these issues, the report concluded.

There was also “insufficient evidence” to compare the accuracy of tests in patients who have risk factors for celiac disease, including family history and type 1 diabetes, as well as those who previously had negative blood test results. Evidence was also lacking in regards to subpopulations of patients, including by race or ethnicity.

More than 83 percent of people living with celiac disease have not been diagnosed. Because family members have up to a 20 percent greater risk for celiac disease than the general public, Beyond Celiac has focused its diagnosis efforts on relatives of those with celiac disease. The Seriously, Celiac Disease educational campaign is designed to inspire individuals with celiac disease to speak with their biological relatives in a research-tested way about asking their doctors for the celiac disease blood test. The campaign will be recognized at the Stanford Medicine X 2016 Conference in September.

More Research Needed

The AHRQ’s evidence-based review of celiac disease is welcome and supports a growing consensus on which blood tests should be used for diagnosis and the role of the biopsy, Dr. Lebwohl said. But he noted there are still many unknowns related to diagnosis and more research is needed.

“There remains a good deal of uncertainty about who to test, including what symptoms should prompt testing for celiac disease and what constitutes a high suspicion that would justify proceeding to a biopsy even in the face of a normal blood test” Dr. Lebwohl said. “Celiac disease is under-diagnosed in the United States, and there is still a great deal of misinformation circulating about celiac disease and gluten.”

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