Small- bowel mucosal changes and antibody responses after low- and moderate-dose gluten challenge in celiac disease

Marja-Leena Lähdeaho,Kaija Laurila,Heini Huhtala,Markku Mäki,Katri Kaukinen

doi:10.1186/1471-230x-11-129

Marja-Leena Lähdeaho, Kaija Laurila + Show 3 more

Open Access

https://doi.org/10.1186/1471-230x-11-129

Copy DOI

Abstract

BackgroundDue to the restrictive nature of a gluten-free diet, celiac patients are looking for alternative therapies. While drug-development programs include gluten challenges, knowledge regarding the duration of gluten challenge and gluten dosage is insufficient.We challenged adult celiac patients with gluten with a view to assessing the amount needed to cause some small-bowel mucosal deterioration.MethodsTwenty-five celiac disease adults were challenged with low (1-3 g) or moderate (3-5g) doses of gluten daily for 12 weeks. Symptoms, small-bowel morphology, densities of CD3+ intraepithelial lymphocytes (IELs) and celiac serology were determined.ResultsBoth moderate and low amounts of gluten induced small-bowel morphological damage in 67% of celiac patients. Moderate gluten doses also triggered mucosal inflammation and more gastrointestinal symptoms leading to premature withdrawals in seven cases. In 22% of those who developed significant small- intestinal damage, symptoms remained absent. Celiac antibodies seroconverted in 43% of the patients.ConclusionsLow amounts of gluten can also cause significant mucosal deterioration in the majority of the patients. As there are always some celiac disease patients who will not respond within these conditions, sample sizes must be sufficiently large to attain to statistical power in analysis.

Highlights

Due to the restrictive nature of a gluten-free diet, celiac patients are looking for alternative therapies
Altogether 25 adult celiac disease patients fulfilling the inclusion criteria were enrolled for the study (Table 1)
The Marsh classification does not take into account minor gluteninduced mucosal changes or discrepant results in villous height crypt depth ratio (Vh/CrD) or intraepithelial lymphocytes (IELs) counts during a gluten challenge

Summary

Introduction

Due to the restrictive nature of a gluten-free diet, celiac patients are looking for alternative therapies. We challenged adult celiac patients with gluten with a view to assessing the amount needed to cause some smallbowel mucosal deterioration. A reduced daily gluten dose (2.5-5 g per day) during a gluten-free diet has still enabled mucosal healing in half of the patients [11]. Some adults challenged with 2.5-5 g of gluten daily for three to 14 months have shown no significant changes in mucosal morphology [12]. These findings are in marked conflict with those from a recent challenge study where it was shown that even a minimal dose of 50 mg gluten daily induced a significant mucosal deterioration [13]. The patient groups in these studies have been rather small and no unequivocal conclusions can be drawn

Methods

Results

Discussion

Conclusion