Intestinal barrier dysfunction during Whipple’s disease

Backround: Classical Whipple’s disease (CWD) is caused by chronic infection with Tropheryma whipplei. Most of the patients suffer from malabsorption and chronic diarrhea accompanied by articular, neuronal, and multisystemic affections. Immunologically, the disease is characterized by a dichotomy of mucosal immune suppression and systemic immune activation. Today, especially mechanisms of diarrhea are largely unknown. To understand underlying pathomechanisms we characterized the mucosal barrier function and possible links to chronic systemic immune activation in CWD-patients.

Methods: Data of 73 CWD patients were compared to the results of 101 control subjects. Small intestinal biopsies or biopsy supernatants, respectively, were studied for villous length, epithelial cell turnover and inflammatory response. In sera markers of microbial translocation such as LPS and activation-associated mediators and cytokines were determined.

Results: In duodenal specimens of CWD patients compared to healthy subjects villus atrophy, increased apoptosis of epithelial cells, and goblet cell hyperplasia indicated barrier dysfunction. In sera of CWD patients intestinal barrier dysfunction becomes evident as enhanced values of LPS in the sera as a marker of microbial translocation indicate microbial translocation. Enhanced values of soluble CD14 in duodenal biopsy supernatants and elevated serum concentrations of soluble CD14 and LPS binding protein hint a gut microbiota driven immune response.

Conclusion: CWD patients exhibit intestinal barrier dysfunction that might provoke diarrhea with subsequent microbial translocation and systemic immune activation at time of diagnosis.