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Celiac Disease Diagnosis: Is a Biopsy Always Necessary?

By: Peter Olins, PhD on May 9, 2013

Although an accurate celiac disease diagnosis is not possible with a single blood test, a recent study has found that a combination of three commercial tests might be able to eliminate the need for a biopsy in 78% of cases.

Diagnosing celiac disease takes skill, because the symptoms are variable and can also result from other conditions. Ideally, there would be a simple blood test for the diagnosis of celiac disease, but for most people, current guidelines require taking a small biopsy from the small intestine. Of course, many people are reluctant to have a biopsy, so there is a strong need to develop a definitive blood test. A recent paper by Burgin-Wolff et al. (Ref. 1) compared the results of six different blood tests with the biopsy results for 149 celiac disease patients and 119 control subjects. Patients with a positive reading in a combination of three tests were found to have a 99% chance of having celiac disease.

False Positives and False Negatives in Celiac Disease Diagnosis

A key issue with all diagnostic tests is the concern about “false positives” and “false negatives”:

  • A “false positive” may result in unnecessary extra interventions, until it is realized that the test was wrong. In the worst case, someone might be diagnosed with celiac disease and then forced to adopt a lifelong gluten-free diet for no reason. In reality, if a false positive blood test is followed up by a biopsy, then the error can be easily exposed and remedied.
  • A “false negative” diagnosis is worse, since a patient may miss out on the benefits of a gluten-free diet, and potentially suffer long-term damage as a result. This is why clinicians work so hard to develop tests and procedures that can give an accurate result.
  • An intestinal biopsy remains the “gold standard” for diagnosis of celiac disease, but even this has the possibility of problems.

Celiac Disease Biopsy—the Pros:

  • Symptoms of celiac disease vary between patients, and can be caused by other conditions; but a biopsy is generally definitive for diagnosing celiac disease.
  • Severe damage of the intestinal lining (villous atrophy) is a serious condition, and undiagnosed disease may lead to permanent health problems.

Celiac Disease Biopsy—the Cons:

  • Preparing and interpreting biopsy samples is a highly skilled activity, so there may be a significant number of false-negative diagnoses.
  • Some doctors may not follow celiac disease guidelines for taking a sufficient number of samples to get an accurate diagnosis.
  • Celiac disease can be “patchy”, affecting only parts of the intestine, meaning that the disease can be missed.
  • During the early phase of celiac disease development, the small intestine may still be healthy and only later develop full-blown celiac disease.
  • Biopsy is expensive, and is not always readily available to all patients.
  • Some people refuse a biopsy, because they fear the procedure.
  • It can be traumatic for infants and children.

Increased Accuracy by Combining Multiple Blood Tests for Celiac Disease

A recent paper by Burgin-Wolff, Mauro and Faruk (Ref. 1) examined the reliability of a variety of blood tests in detecting celiac disease, using blood from 149 celiac disease patients, compared with the results from 119 healthy control subjects. Patients and control subjects were from a wide variety of clinics in Germany, Austria and Switzerland.

Several combinations of  commercial antibody tests were examined to see which produced the most reliable results (i.e. the minimum number of false-negative diagnoses without a significant number of false-positives). The following six celiac disease diagnostics were compared:

  • anti-tissue transglutaminase IgA (anti-tTG measures an autoimmune response triggered by gluten)
  • anti-EMA IgA (this has very similar specificity to anti-tTG)
  • anti-gliadin—both IgA and IgG (this is an older diagnostic that is still used sometimes)
  • anti-deamidated gluten peptide—both IgA and IgG (anti-DGP tests were recently introduced)

The authors compared the results of various combinations of two or more diagnostic tests, looking at which tests gave a value outside the normal range. They found that 78% of the patients in their study with celiac disease gave a positive signal with a combination of three tests (anti-tTG IgA and anti-DGP (both IgA and IgG). This combination was about 99% accurate in diagnosing celiac disease in these people.

Celiac Disease Diagnosis

Anti-Gliadin Antibodies Provided No Useful Information

These antibodies were the first to be introduced, several years ago, but they give a large number of false-positives.

Anti-Endomysium Antibody Provides Little Further Benefit

The anti-EMA test is widely used for celiac disease diagnosis, because it is very specific (very few false positives). However, using the new 3-test combination, no further benefit was achieved by adding the anti-EMA test. This is fortunate, since the EMA test is more expensive, and requires interpretation by a skilled technician, since it cannot be automated.


Ref. 1: Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests. BMC Gastroenterol. (2013) 13:9 doi: 10.1186/1471-230X-13-19 Burgin-Wolff, A et al.

Possible Concerns and Limitations of the Study:

  • Most studies in this field involve patients who already have symptoms which are strongly suggestive of celiac disease. This means that the tests may be less accurate in cases where the original symptoms are less clear.
  • Studies like this only rely on a small number of patients, so it is hard to extrapolate these results to the needs of millions of potential patients.
  • This is still an experimental approach and needs to be confirmed in other laboratories before becoming routine.

Summary of Key Points

  • A recent study compared the results of blood diagnostics of 149 celiac disease patients with those 119 healthy control subjects.
  • Six types of available diagnostic assays were compared, to see which were most predictive of actual disease: anti-tTG (IgA), anti-gliadin (IgA), anti-deamidated gluten peptide (both IgA and IgG), anti-gliadin (both IgA and IgG) and anti-endomysium (IgA).
  • The best combination of fewest false-negatives with fewest false-positive diagnoses was achieved with a combination of three tests delivering the diagnostic “sweet spot” (the three antibodies were anti-tTG IgA, anti-deamidated gluten peptide IgA, and anti-deamidated gluten peptide IgG).
  • All the patients who were positive for all three tests could be correctly diagnosed without the need to resort to biopsy.
  • This means that biopsy could have been avoided for 78% of celiac disease patients, without compromising their diagnosis.
  • The older anti-gliadin antibody test provides no addition information when added to more recent diagnostics.
  • Anti-endomysium was found to offer no advantages over anti-tTG.


Celiac disease diagnosis can be reliably achieved in a large fraction of patients (78%), without the need to resort to a biopsy for confirmation, using a combination of three simple antibody tests.

As always, this blog is offered for informational purposes: always consult a qualified physician to determine the options available for celiac disease diagnosis.

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