Noninvasive Markers of Gluten Ingestion in Celiac Disease Patients

The gold-standard for monitoring of dietary adherence is consultation with an expert
dietitian, but this may be time-consuming for patients and local expertise may not be
available. Intestinal biopsy is the only direct method to document mucosal healing and can
be considered in all adults with celiac disease. Non-invasive assessment of compliance with
a gluten free diet(GFD) can be achieved with monitoring of IgA antibodies to tissue
transglutaminase (IgA-tTG) or deamidated gliadin peptides, as these markers improve with
gluten elimination. However, intestinal mucosal damage is present in a significant number of
patients who report compliance with a gluten free diet and have normalized serology,
potentially due to dietary lapses or unrecognized contamination with gluten. Furthermore,
serologic testing may be normal in patients with partial adherence. Patient reported surveys
show promise for assessing gluten free diet adherence, but further studies are needed.

Intestinal fatty acid-binding protein (I-FABP), a small (15 kD) cytosolic protein found
exclusively in the small bowel enterocytes, has been studied as a marker of intestinal
epithelial damage in septic shock and mesenteric ischemia. More recently, elevated levels of
intestinal fatty acid-binding protein( I-FABP) have been described as a marker of intestinal
injury in both adults and children with celiac disease. Intestinal fatty acid binding
protein, (I-FABP) levels have been shown to significantly correlate with the degree of
villous atrophy and IgA antibody to tissue transglutaminase (IgA-tTG), as well as decrease
upon treatment with a gluten free diet(GFD). Incomplete normalization of intestinal fatty
acid binding protein(I-FABP) on a gluten free diet points to ongoing intestinal injury, even
in the absence of circulating antibodies, thus suggesting its potential as a non-invasive
marker for gluten free diet adherence and intestinal damage in celiac disease.

The measurement of gluten immunogenic peptides (GIP) in stool is a novel method to monitor
gluten free diet compliance. Recently, a technique to detect gliadin 33-mer equivalent
peptide epitopes (33EPs) in the stool of pediatric patients has been described. These
peptides show significant resistance to digestion and were detected in healthy individuals
after normal gluten-containing diet ingestion. Importantly, these peptides are not detected
in patients on a gluten free diet, and there appears to be a correlation between the amount
of gluten intake and the peptide levels. A similar test has been developed for gluten
intestinal peptide(GIP) detection in urine, although there are currently no peer-reviewed
studies examining this technique. Further research on the utility of stool and urine gluten
intestinal peptide (GIP)for monitoring of gluten free diet (GFD) adherence is warranted.

Given the lack of a non-invasive and accurate measure of gluten intake in celiac disease
(CD), the investigators will investigate the effect of gluten intake in celiac disease (CD)
patients using a variety of markers. Patients who are symptom-free on a gluten free diet
(GFD) will be exposed to various amounts of gluten. Factors that will be studied include the
effect on patient estimated gluten intake, Celiac disease symptoms, IgA-tTG level,intestinal
fatty acid binding protein( I-FABP) level, and both stool and urine gluten peptide levels.

Inclusion Criteria:

- This study population will consist of patients with a prior diagnosis of celiac
disease based on intestinal biopsy (Marsh score of 1-4) who report control of
symptoms with adherence to gluten free diet(GFD) for at least one year and have a
baseline IgA antibody to tissue transglutaminase(IgA-tTG) within the normal range.

Exclusion Criteria:

- Patients < 18 years of age

- Patients with refractory celiac disease (RFD), defined as persisting or recurring
symptoms and mucosal villous atrophy, despite strict adherence to a gluten free diet
(GFD) for >12 months and a negative IgA antibody to tissue transglutaminase (IgA-tTG)

- Patients with enteropathy-associated T-cell lymphoma

- Patients with IgA deficiency

- Patients with a diagnosis of inflammatory bowel disease, irritable bowel symptoms, or
acute gastroenteritis

- Patients taking immunosuppressive medications

- Patients who are pregnant

- Patients who are breast feeding/lactating