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Improving Celiac Disease Testing — I-FABP

By: Peter Olins, PhD on February 3, 2012.

An improved celiac disease test is required. Conventional assays for anti-tissue transglutaminase 2 (TGT-2) and endomysial antibody (EMA) in the blood can miss a substantial number of cases (Ref. 1). In addition, there is no reliable way to monitor compliance with a gluten-free diet. Recent studies (Ref. 2) indicate that measuring the amount of the protein I-FABP in the blood may provide a useful tool to supplement the currently accepted assays.

Current diagnostic blood tests miss many cases of celiac disease

1.  ChildrenAlternative Approach for Celiac Disease Testing

Early diagnosis of celiac disease is important, since the damage to the intestine can cause major nutritional deficiencies. However, for a significant number of children with celiac disease, the current serum antibody tests are not always definitive (Ref. 3), so the more invasive approach of an intestinal biopsy may be necessary.

2.  ”Hidden” celiac disease in adults

Not all celiac disease shows up in a typical blood test, in other words, there are “false-negatives”. In one study, many family members of people with celiac disease had anti-TGT-2 deposits in the lining of their intestines, but their blood tests were negative (Ref. 4), and they had normal results from an intestinal biopsy. However, their symptoms improved after going on a gluten-free diet, suggesting that a negative blood test for anti-TGT-2 may not necessarily rule out celiac disease.

3.  Older adults

Older patients often do not have the typical gastrointestinal symptoms seen in younger people; instead, symptoms can show up in many different parts of the body, making diagnosis harder. In addition, the EMA test is less effective at detecting celiac disease in older adults. One study found that the EMA assay was 98% successful in identifying CD in patients under 35 years old, but only 80% effective in older patients (Ref. 5).

4.  Monitoring dietary compliance with a gluten-free diet

A strict gluten-free diet is vital for celiac patients, but it is hard for a physician to know whether a patient has been consuming gluten (either deliberately or as a result of accidental contamination). Although the anti-TGT-2 blood test is typically used for the initial celiac disease diagnosis, once a patient goes on a gluten-free diet, the test is not effective for detecting the damage caused by small amounts of gluten in the diet (Ref. 6).

I-FABP (Intestinal Fatty Acid Binding Protein) — an additional  diagnostic approach for celiac disease testing

I-FABP is a protein normally found in the lining of the small intestine. Various kinds of damage to the intestine cause I-FABP to be released into the bloodstream (Ref. 2), so there has been considerable interest in finding out whether this is also true for celiac disease. In two recent studies from Maastricht University in the Netherlands, researchers investigated the use of I-FABP as an indicator of the intestinal damage caused by CD.

Forty-nine children with biopsy-proven CD were tested for I-FABP levels before going on a gluten-free diet (ref. 7). The test was 98% effective at confirming CD. Interestingly, the levels of protein could be used to predict the degree of damage to the intestine (villous atrophy), opening up the possibility of using the test as a tool for monitoring compliance with a gluten-free diet.

As mentioned earlier (Ref. 4), anti-TGT-2 can be present as deposits in the the intestine, but absent from blood. Recent research has shown that this “hidden” celiac disease still results in substantial levels of I-FABP in the bloodstream (Ref. 7), suggesting that an assay for I-FABP could help in uncovering cases of celiac disease that might otherwise have been missed.

This work is still at the research stage, so there is no diagnostic test available for the general public yet, but this is definitely a field that we will be following. It should be noted that high serum I-FABP levels also occur in a variety of intestinal conditions, but the assay may be a useful addition to the tools currently available for diagnosing and monitoring celiac disease.


Ref. 1:  Li, M, et al. Am J Gastroenterol. 2009 Jan;104(1):154-63.A report on the International Transglutaminase Autoantibody Workshop for Celiac Disease.

Ref. 2:  Funaoka, H, et al.  Immunol Invest. 2011;40(3):223-42. Epub 2011 Jan 4. Development of a high-specificity sandwich ELISA system for the quantification of human intestinal fatty acid-binding protein (I-FABP) concentrations.

Ref. 3:  Parizade, M & Shainberg, B.  CLINICAL AND VACCINE IMMUNOLOGY, 2010, p. 884–886 Vol. 17, No. 5. Positive Deamidated Gliadin Peptide Antibodies and Negative Tissue Transglutaminase IgA Antibodies in a Pediatric Population: To Biopsy or Not To Biopsy.

Ref. 4:  Close relatives of celiac disease patients show gluten-sensitivity without diagnosed celiac disease.

Ref. 5:  Boger, CP et al.  Eur J Gastroenterol Hepatol. 2007 Oct;19(10):890-5. Determinants of endomysial antibody status in untreated coeliac disease.

Ref. 6:  Vahedi, K, et al. Am J Gastroenterol. 2003 May;98(5):1079-87. Reliability of antitransglutaminase antibodies as predictors of gluten-free diet compliance in adult celiac disease. 

Ref. 7:  Vreugdenhil, AC Scand J Gastroenterol. 2011 Dec;46(12):1435-41. Epub 2011 Oct 27.  Additional value of serum I-FABP levels for evaluating celiac disease activity in children.
Ref. 8:  Not, T, et al.  Gut doi:10.1136/gut.2010.232900  Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet.

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