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Goodbye Biopsy? Non-Invasive Celiac Disease Blood Test Using I-FABP

By: Peter Olins, PhD on February 4, 2014.

Despite progress in blood tests, celiac disease is still hard to diagnose definitively, and about 85% of cases in the U.S. are still undiagnosed. In a new research study from the University of Maastrich, in the Netherlands, scientists have developed a new blood test that may be able to measure intestinal damage without the need to perform a biopsy.

We Still Need Better Tests for Diagnosing Celiac Disease and for Monitoring Recovery

Current blood tests for celiac disease are not ideal. They rely on the presence of antibodies that react with the patient’s own proteins (anti-TTG or anti-EMA antibody tests). However, these tests are most accurate when a patient is consuming substantial amounts of gluten: if a patient has already gone on a gluten-free diet, a doctor will usually want to do a lengthy “gluten challenge”.

Problems With a Gluten Challenge

The whole concept of a gluten challenge seems a little barbaric, since it involves deliberately causing damage to the small intestine over a period of weeks or months. For some people this can be an ordeal, since this can involve unpleasant or painful side effects. I can’t think of any other diseases in which a doctor deliberately provokes substantial damage to the body. For example, a doctor does not diagnose heart disease by deliberately provoking a heart attack! In some ways, celiac disease can be thought of as the “end-stage” of an immune reaction that may have been developing over a long period of time.

In addition, since celiac disease can take a long time to heal, some people may even question the ethics of a using a gluten challenge.

Monitoring Compliance on a Gluten-Free Diet is Still Difficult

Currently, there are two ways to monitor if a patient has been successful in avoiding gluten—a blood test or biopsy—but neither of these approaches is ideal. The simplest approach is to measure the reduction in levels of auto-antibodies. While this gives an indication of progress, there can still be remaining intestinal damage even when the antibody levels have gone back to normal.

Celiac Disease Biopsy is Problematical

The other approach is to do a repeat biopsy, but this also has its problems. Biopsy can be unpleasant for some people; in fact, many people have told me that they have not even been tested for celiac disease because a biopsy is often required for a diagnosis. Biopsy also carries a small risk of complications, it is expensive, the samples require highly-skilled interpretation, and it is not completely accurate in measuring intestinal healing. In addition, physicians are still hesitant to order a biopsy evaluation, or to request that a sufficient number of samples be taken.

Monitoring Intestinal Damage With a Blood Test for I-FABP (Intestinal Fatty Acid Binding Protein)

Two years ago, I described some fascinating research by a Dutch group on the use of I-FABP (intestinal fatty acid binding protein) as a potential diagnostic marker for intestinal damage in 49 children with biopsy-proven celiac disease. This protein is normally present in the cells lining the small intestine, but it leaks into the bloodstream if the cells are damaged. The results looked promising, suggesting that I-FABP might be used for monitoring the disease.

Considerable progress has been made in this work (Ref. 1). A recent paper by MP Adriaane and co-workers tested the blood levels of I-FABP in 96 biopsy-proven patients with active celiac disease, and compared them with 114 healthy individuals. They found that the patients with the greatest degree of intestinal damage (measured by biopsy or anti-TTG levels) had the highest levels of I-FABP in their blood. In other words, the I-FABP values could potentially be used as measure of damage. On average, the active celiac patients had about a 4-fold increase in I-FABP.

Ref. 1: MP Adriaanse, et al.  Aliment Pharmacol Ther. 2013 Feb;37(4):482-90. doi: 10.1111/apt.12194. Epub 2013 Jan 7. Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies.

Patients on a Gluten-Free Diet Had Lower Blood Levels of I-FABP

Sixty-nine celiac patients were then tested for I-FABP levels after going on a gluten-free diet. As expected, the I-FABP levels for the group dropped significantly. However, it was intriguing that the average level for the group was still measurably higher than that found in healthy individuals. In contrast, the levels of anti-TTG antibodies—commonly used as a way of monitoring compliance with a gluten-free diet—had dropped into the normal range. When the individual patients with raised I-FABP levels were re-examined by biopsy, it was found that they were still not responding fully to the GF diet. In other words, the I-FABP test seems to be a sensitive test for residual cellular damage.

Goodbye, Biopsy; Hello Blood-Test?

These results are exciting, because it would be much easier to screen for intestinal healing relying on repeated blood tests, rather than an occasional biopsy.

Sadly, this work is still at the research stage, and will need to be validated by other laboratories with a larger number of patients. If the results hold up, it seems likely that it would not be hard to develop a diagnostic test that could be requested by doctors. Let’s hope that this approach can be developed commercially, and that the “gold-standard” of requiring a biopsy for a celiac disease diagnosis can become a thing of the past.

4 comments to Goodbye Biopsy? Non-Invasive Celiac Disease Blood Test Using I-FABP

  • anne

    We have some excellent tests for coeliac and non-coeliac gluten sensitivity plus cross reactivity. They are run by [ad. removed]. Available via [ad. removed] in the UK. These are the real cutting edge tests.

    • Peter

      Hi Anne —

      Normally, we approve blog comments unedited, but in this case, your comment was more of an advertisement.

      Currently, the mechanism of non-celiac gluten sensitivity is unknown, and there are, unfortunately, no valid diagnostic tests. This is an active area of basic research, but in the mean time, I cannot support the sale of diagnostic tests in the U.S. that are not approved by the FDA. Perhaps the regulations are different in the U.K., but I would still want to see the data before endorsing them.

      I agree that “cross-reactivity”is a fascinating hypothesis (in this case, the idea that the immune response to gluten will also respond to other foods). However, at this point, there is little published evidence to support this concept, let alone a commercial diagnostic.

  • fred brouns

    dear PETER ET AL
    ALTHOUGH the mechanism of non-celiac gluten sensitivity is unknown AS WRITTEN WE DO KNOW THAT NCGS is not related to signs of intestinal damage.
    celiac disease does cause damage and does increase I FABP. HOwever, all cases of intestinal damage do, incl. cancer, ischemic damage, etc. THUS I FABP is not specific for celiac disease and as such an inappropriate marker . IN case of biopsy proven celiac damage IFABP can be used however, to follow recovery form celiac disease symptoms

    • Peter

      Hi Fred, Good to hear from you, again.

      You raise some important points.

      While I agree that we don’t know enough about NCGS, there have been biopsies done on a number of NCGS patients, and all had normal intestinal villi (Marsh grade 0) or slight lymphocyte infiltration (Marsh 1). (e.g. http://www.biomedcentral.com/content/pdf/1471-230X-14-26.pdf, http://www.ncbi.nlm.nih.gov/pubmed/22825366, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724402/, http://www.biomedcentral.com/1741-7015/9/23 )
      I was not meaning to imply in the article that the I-FABP test would be suitable for NCGS.

      Intestinal Damage:
      I agree that more than one kind of intestinal damage can result in raised I-FABP levels; however, I would argue that anyone showing raised levels would deserve further medical investigation, regardless of the cause. I wasn’t proposing that I-FABP would be used as a primary screen. However, as I pointed out, the assay has a number of potential advantages: 1) as a blood test it would be much more likely to be used by physicians than a biopsy, 2) it would be much more acceptable to patients, increasing the likelihood of getting a diagnosis, 3) biopsy/histology suffers from a significant number of false-negatives, and 4) the I-FABP assay appears to more sensitive than the current antibody tests for monitoring recovery on a GF diet.

      Finally, I would be especially interested to see how the I-FABP assay performs for older people, since for an unknown reason, older people are more likely to have intestinal damage without raised celiac-specific antibody levels, and are therefore less likely to be diagnosed correctly.

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