A comparison of antibody testing, permeability testing, and zonulin levels with small-bowel biopsy in celiac disease patients on a gluten-free diet.

Active celiac disease is associated with positive endomysial (EMA) and tissue transglutaminase (TTG) antibodies, elevated zonulin levels, and increased intestinal permeability. There is little known about what happens to these immunologic and structural abnormalities in patients on a gluten-free diet and their correlation with small-bowel biopsy changes. Adult patients previously diagnosed with celiac disease and on a gluten-free diet for greater than 1 year were considered for the study. All patients underwent the following: measurement of EMA and TTG antibodies, serum zonulin levels, intestinal permeability (IP) testing with lactulose/mannitol ratios, food diary analysis for gluten ingestion and small- bowel biopsy. A total of 21 patients on a gluten-free diet for a mean of 9.7 years completed the study. There were ten patients who had normalization of intestinal biopsies, IP and TTG, and EM antibodies. Six patients had Marsh type 2 or 3 lesions and all had either abnormal IP (5/6) or TTG antibody (4/6). In patients with Marsh type 3 lesions, there was a correlation between IP and zonulin levels. A subgroup of patients with celiac disease on a gluten-free diet has complete normalization of intestinal biopsies, intestinal permeability defects, and antibody levels. Patients with Marsh type 3 lesions have abnormal TTG antibodies and intestinal permeability with zonulin levels that correlate with IP. These abnormalities may be due to continued gluten ingestion. Further study is needed to determine the clinical utility of TTG antibodies and IP testing in following patients with celiac disease.

Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet.

Intestinal permeability is frequently abnormal in patients with celiac disease. The long-term effect of a gluten-free diet on intestinal permeability and the correlation of intestinal permeability with a gluten-free diet are not known. The objectives of this study were to determine the responses of intestinal permeability and antibody testing to gluten free diet and the degree of correlation of these measurements with gluten ingestion. In this prospective study, patients with celiac disease were divided into three groups based on length of time on a gluten-free diet: Group A, < 1 month; Group B, 1 month-1 year; Group C, > 1 year. Patients in Groups B and C were tested at baseline and at 4-12 weeks later for the following: lactulose/mannitol intestinal permeability, endomysial antibody, and 3-day food record. Permeability tests were also performed in Group A and control subjects. Intestinal permeability was elevated in newly diagnosed celiac disease and in individuals on a gluten-free diet for less than 1 year. Intestinal permeability was normal in 80% at visit 1 and 87% at visit 2 in individuals with celiac disease on a gluten-free diet for more than a year. Trace gluten ingestion was associated with increased intestinal permeability on visit 2 (P = 0.0480). The sensitivity of detecting gluten ingestion as measured by a 3-day food record was higher for permeability testing (29 and 36%) compared with endomysial antibody testing (18 and 18%) for visits 1 and 2, respectively. Intestinal permeability normalizes in the majority of individuals with celiac disease on a gluten-free diet. Gluten ingestion as measured by a 3-day food record correlates with intestinal permeability measurements. The role of permeability testing in the follow-up of patients with celiac disease warrants further investigation.