Architectural and functional alterations of the small intestinal mucosa in classical Whipple's disease
| Autor: | Kristina Allers, Susanne M. Krug, H. J. Epple, Britta Siegmund, Verena Moos, Anja Fromm, Michael Fromm, Thomas Schneider, Julian Friebel, Joerg-Dieter Schulzke, Hanno Troeger, Katina Schinnerling |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty Malabsorption Duodenum animal diseases Immunology Apoptosis Inflammation Systemic inflammation Tight Junctions Young Adult 03 medical and health sciences 0302 clinical medicine Intestine Small medicine Humans Immunology and Allergy Whipple's disease Intestinal Mucosa Immunity Mucosal Barrier function Aged Gastrointestinal tract Hyperplasia Interleukin-13 Tight junction Tumor Necrosis Factor-alpha business.industry Middle Aged medicine.disease MARVEL Domain Containing 2 Protein 030104 developmental biology Claudins Female 030211 gastroenterology & hepatology Tumor necrosis factor alpha Atrophy medicine.symptom business Whipple Disease |
| Zdroj: | Mucosal Immunology. 10:1542-1552 |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2017.6 |
| Popis: | Classical Whipple's disease (CWD) affects the gastrointestinal tract and rather elicits regulatory than inflammatory immune reactions. Mechanisms of malabsorption, diarrhea, and systemic immune activation are unknown. We here analyzed mucosal architecture, barrier function, and immune activation as potential diarrheal trigger in specimens from 52 CWD patients. Our data demonstrate villus atrophy and crypt hyperplasia associated with epithelial apoptosis and reduced alkaline phosphatase expression in the duodenum of CWD patients. Electrophysiological and flux experiments revealed increased duodenal permeability to small solutes and macromolecules. Duodenal architecture and permeability ameliorated upon antibiotic treatment. Structural correlates for these alterations were concordant changes of membranous claudin-1, claudin-2, claudin-3, and tricellulin expression. Tumor necrosis factor-α and interleukin-13 were identified as probable mediators of epithelial apoptosis, and altered tight junction expression. Increased serum markers of microbial translocation and their decline following treatment corroborated the biological significance of the mucosal barrier defect. Hence, mucosal immune responses in CWD elicit barrier dysfunction. Diarrhea is caused by loss of absorptive capacity and leak flux of ions and water. Downregulation of tricellulin causes increased permeability to macromolecules and subsequent microbial translocation contributes to systemic inflammation. Thus, therapeutic strategies to reconstitute the mucosal barrier and control inflammation could assist symptomatic control of CWD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink