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Defective tight junctions in refractory celiac disease.
Michael Schumann1, Sarah Kamel, Marie-Luise Pahlitzsch
1Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Germany. michael.schumann@charite.de
Annals of the New York Academy of Sciences
|June 27, 2012
Summary
Refractory celiac disease involves altered gut barrier proteins, specifically downregulation of claudin-4 and claudin-5, and upregulation of claudin-2. These changes impact the intestinal epithelial barrier in non-responsive celiac disease patients.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Celiac disease involves immune activation against gluten, leading to small intestinal mucosal atrophy.
- While typically managed with a gluten-free diet, a subset of patients develop refractory celiac disease.
- Epithelial barrier defects are implicated in celiac disease, but their role in refractory cases remains unclear.
Purpose of the Study:
- To investigate the functional and structural integrity of the tight junction-associated epithelial barrier in refractory celiac disease.
- To identify specific claudin protein alterations in the intestinal mucosa of refractory celiac disease patients.
Main Methods:
- Functional and structural analysis of the epithelial barrier.
- Assessment of claudin protein expression and localization.
- Investigation of claudin endocytosis mechanisms.
Main Results:
- Claudin-4, normally expressed in celiac disease, is downregulated in refractory cases.
- Downregulation of claudin-4 appears to result from reduced protein expression and increased endocytosis.
- Claudin-5 expression is downregulated, while pore-forming claudin-2 is upregulated in refractory celiac disease.
Conclusions:
- The epithelial barrier is significantly altered in refractory celiac disease, beyond typical celiac disease.
- Specific changes in claudin expression (downregulation of claudin-4 and -5, upregulation of claudin-2) characterize the refractory state.
- These claudin alterations likely contribute to the persistent inflammation and barrier dysfunction in refractory celiac disease.
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