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23-05-2012 | Genetics | Article

Low-level gluten challenge provokes celiac response


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MedWire News: Significantly less gluten is required to induce a clinically measurable response in patients undergoing testing for celiac disease than previously thought, say US researchers.

Just 3 g per day for 2 weeks elicited gastrointestinal symptoms, duodenal changes, and increased antibody titers in most celiac patients who had previously been gluten-free, reports the team from Beth Israel Deaconess Medical Center in Boston, Massachusetts.

This compares with the standard gluten challenge of two servings a day for 8 weeks, which is unpopular with patients due to intolerable symptoms over the extended period of time, explain Daniel Leffler and co-workers.

The team randomly assigned 20 adults with biopsy-proven celiac disease, who had been gluten-free for at least 1 year, to receive 3 g or 7.5 g of gluten daily for 2 weeks. The patients were examined at baseline, 3, 7, 14, and 28 days after beginning the gluten challenge.

One patient was excluded from the trial due to a genetic profile not supportive of a celiac disease diagnosis. Of the 19 remaining patients in the study, 17 (89.5%) met the criteria for celiac disease diagnosis by the end of the 2-week gluten challenge.

Duodenal biopsy at baseline and day 14 demonstrated a significant decrease in the ratio of villous height to crypt depth (2.2 to 1.1), and a significant increase in the intraepithelial lymphocyte count (32.6 to 51.8 per 100 enterocytes).

Patients also experienced a marked increase in levels of antibodies against tissue transglutaminase and deamidated gliadin peptides between baseline and day 14, although this did not reach statistical significance. Levels continued to rise after the challenge was completed.

By day 3 of the study, patients reported a significant increase in gastrointestinal symptoms, such as diarrhea or fatigue, measured using the Celiac Symptom Index, and the Gastrointestinal Symptom Rating Scale. Symptoms returned to baseline values by day 28 of the study.

The extent of these biopsy and antibody changes did not significantly differ between the 3 g and 7.5 g treated patients, nor between patients who had been gluten-free for less than or more than 48 months, the team notes.

However, the lactulose to mannitol ratio (LAMA), a marker of small intestine passive permeability, did not significantly change over the study period in either patient group.

The researchers observe that the timing of intestinal changes did not significantly correlate with those of serology, symptoms, or LAMA.

"If we accept that duodenal mucosal damage is the gold standard marker of coeliac disease activity, then it is clear that, despite out encouraging findings, improved non-invasive markers of coeliac disease activity are greatly needed for use in patient management and clinical research," emphasize Leffler et al writing in Gut.

Finally, noting that a minority of patients had no significant response to the 2-week gluten challenge, and that gluten sensitivity varied significantly among the group, they conclude: "An accurate, non-invasive measure of coeliac disease activity would be valuable in many respects and may allow the strictness of the gluten-free diet to be personalised without negative consequences. "

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Lynda Williams

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