Introduction
In celiac disease (CeD), it is known that damage to the duodenal mucosa occurs as a consequence of a T-lymphocyte-triggered immune reaction, leading to epithelial barrier defects1,2. In addition to this adaptive immune response, intraepithelial lymphocytes are known to play a role in generating the epithelial lesion in CeD as their Natural Killer (NK) receptors are able to recognize atypical MHC-expressing enterocytes2. However, the timing of onset of epithelial barrier defects is still far from clearly understood3,4.
Aims & Methods
The aim of the study was to observe if, in CeD, gluten exposure of the duodenal mucosa generates rapid epithelial barrier changes. Confocal laser endomicroscopy (CLE) allows the observation of the mucosal epithelia in vivo5. CeD patients and controls undergoing gastroscopy were examined with CLE before and after exposing the duodenal mucosa to a gluten-containing solution applied with a spraying catheter. All CeD patients were on a long-term gluten-free diet and had negative transglutaminase antibodies at the time of the CLE examination. Fluorescein, which has molecular size of 330 Dalton, was administered intravenously at the beginning of the examination. The presence of an epithelial barrier defect was defined if fluorescein passed from the mucosal capillaries to the lumen.
Results
Eight CeD patients and seven controls were included. In none of the 15 subjects a barrier defect was observed at the CLE after administration of fluorescein and before duodenal exposure to gluten. After gluten exposure, signs of a barrier defect, such as a fluorescein in the lumen or transepithelial fluorescein leaks, were observed in seven out of eight CeD patients (88%). The median time from gluten exposure to the detection of the barrier defect was 20 minutes (range 15-30 minutes). No signs of fluorescein leak were detected after gluten exposure of the eight controls after a median observation of 30 minutes.
Conclusion
A rapid occurrence of a gluten-induced barrier defect, as early as within 15 minutes after gluten exposure, was observed in vivo in CD patients.
This observation suggest the possibility that innate immune mechanisms, rather than the activation of gluten-specific T-cells, might play a role in such a rapid onset of this barrier leak.
References
1. Jabri B, Sollid LM. T Cells in Celiac Disease. The Journal of Immunology. 2017;198(8):3005-3014. doi:10.4049/jimmunol.1601693
2. Hüe S, Mention JJ, Monteiro RC, et al. A Direct Role for NKG2D/MICA Interaction in Villous Atrophy during Celiac Disease. Immunity. 2004;21(3):367-377. doi:10.1016/j.immuni.2004.06.018
3. Schumann M, Günzel D, Buergel N, et al. Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in coeliac disease. Gut. 2012;61(2):220-228. doi:10.1136/gutjnl-2011-300123
4. Schumann M, Siegmund B, Schulzke JD, Fromm M. Celiac Disease: Role of the Epithelial Barrier. Cell Mol Gastroenterol Hepatol. 2017;3(2):150-162. doi:10.1016/j.jcmgh.2016.12.006
5. Günther U, Daum S, Heller F, et al. Diagnostic value of confocal endomicroscopy in celiac disease. Endoscopy. 2010;42(03):197-202. doi:10.1055/s-0029-1243937