Serum Markers in Gluten Challenge

The diagnosis of celiac disease carries with it important ramifications. Celiac disease is a systemic immunologic disorder in which the sentinel lesion is an enteropathy triggered by polypeptides derived primarily from the gliadin proteins found in wheat, rye and barley. Ingestion of the offending proteins leads to inflammation and intestinal mucosal damage, which results in a spectrum of abdominal symptoms, increased intestinal permeability, malabsorption, occult gastrointestinal bleeding and diarrhea. Systemic manifestations of celiac disease include a myriad of conditions including malignancy and autoimmune disease.

The only accepted treatment for celiac disease is lifelong adherence to a gluten free diet. Adherence to this diet, simply put avoiding all foods containing even small amounts of wheat, rye and barley, has been shown to lead to improvement in the majority of related problems and normalization of all standard diagnostic tests. Because of this many individuals who present for evaluation of possible celiac disease but who are already on a gluten free diet cannot be tested accurately as there is currently no way of differentiating between healthy individuals and individuals with well treated celiac disease. The standard practice in such cases is to perform a 'Gluten Challenge' whereby the patient eats the equivalent of 2 slices of bread per day for six to eight weeks before returning for evaluation with serologic testing and endoscopy with duodenal biopsy. The use of the gluten challenge in clinical practice is limited by patient symptoms and resistance to such a long test period, after which it may take a number of weeks for the intestine to heal and the symptoms to resolve. Autoantibodies to tissue transglutaminase or antibodies to deamidated gliadin, while being excellent tools to predict celiac disease in patients who have been on a long-term gluten containing diet, display low sensitivities to detect short-term and/or recent gluten exposure. For this reason, it would be very useful if novel circulating markers could be identified that indicate the presence of celiac disease and in particular would provide an early and less invasive marker of a positive response to gluten challenge.