Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease
- Daniel Leffler1,
- Detlef Schuppan1,
- Kumar Pallav1,
- Robert Najarian2,
- Jeffery D Goldsmith2,
- Joshua Hansen1,
- Toufic Kabbani1,
- Melinda Dennis1,
- Ciarán P Kelly1
- 1Celiac Center and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
- 2Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
- Correspondence to Dr Daniel Leffler, Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA;
Contributors Author involvement: DL, DS and CPK: Study design and execution, analysis of data, writing of manuscript. KP, JH and TK: Study execution. RN and JG: Study execution, analysis of data. MD: Study design, execution and enrolment.
- Revised 27 March 2012
- Accepted 11 April 2012
- Published Online First 22 May 2012
Objective Coeliac disease is defined by gluten responsiveness, yet there are few data on gluten challenge (GC) in adults on a gluten-free diet. Lack of data regarding the kinetics of responses to gluten is a limitation in clinical practice and research when GC is performed.
Design 20 adults with biopsy-proven coeliac disease participated. The study included two run-in visits followed by a 14-day GC at a randomly assigned dose of 3 or 7.5 g of gluten/day. Study visits occurred 3, 7, 14 and 28 days after starting GC. Duodenal biopsy was performed during the run-in and at days 3 and 14 of GC. Villous height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocyte (IEL) count/100 enterocytes were measured by two pathologists. Antibodies to tissue transglutaminase and deamidated gliadin peptides, lactulose to mannitol ratio (LAMA) and symptoms were assessed at each visit.
Results Significant reduction in Vh:Cd (2.2–1.1, p<0.001) and increase in IELs (32.6–51.8, p<0.001) were seen from baseline to day 14. Antibody titres increased slightly from baseline to day 14 of GC but markedly by day 28. LAMA did not change significantly. Gastrointestinal symptoms increased significantly by day 3 and returned to baseline by day 28. No differences were seen between the two gluten doses.
Conclusions 14 day GC at ≥3 g of gluten/day induces histological and serological changes in the majority of adults with coeliac disease. These data permit accurate design of clinical trials and indicate that many individuals will meet coeliac diagnostic criteria after a 2-week GC.
Funding The project described was supported by Grant Number UL1 RR025758-Harvard Clinical and Translational Science Center, from the National Institute of Health, National Center for Research Resources and by National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK082619. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NIH DK1042103881.
Competing interests None.
Ethics approval Ethics approval was provided by BIDMC Committee on Clinical Investigations.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All data are available upon request.