An investigation of Crohn's Disease in the Oral Cavity

• Author / Creator

  Ramadan Elchames, Maison

• Crohn’s disease (CD) is one of the chronic inflammatory bowel diseases (IBD) with a complex etiology involving genetic factors, priming by enteric microflora, environmental factors and a change in the immune-mediated response, the other IBD is ulcerative colitis. The diagnosis of CD has continuously been challenging for physicians and medical practitioners as there is no single ‘‘gold standard’’ test or examination. Instead, physicians apply a combination of symptoms, clinical examination, laboratory indices, radiology, and endoscopy with histology to diagnose the disease. The techniques used for diagnostic decision are considered invasive, expensive, and time-consuming; therefore, an ideal non-invasive test is increasingly expected for initial diagnosis and identification of disease activity and the early determination of diagnosis and detection of disease activity are essential for tailoring therapy. Noninvasive specimen collection and analysis to help physicians distinguish CD would allow more rapid and appropriate treatment, as well as the potential to improve quality patient care while reducing both direct and indirect associated cost through the elimination of unnecessary procedures and more efficient medical treatment. It is well accepted that CD patients have an impaired intestinal epithelial barrier function. This allows the luminal microbiota to position themselves within close proximity of the intestinal epithelium inside the mucous layers. Furthermore, the gaps within the epithelial cell layer permit microbes to invade the intestinal tissues. This invasion triggers the dysregulated immune response characteristic of CD. Recent identification of elevated levels of caspase-1, an integral component of the inflammasome involved in pyroptosis, has been reported. In turn, this has been associated with the increased number of epithelial gaps in the epithelial layer relative to healthy controls. A systematic literature review was conducted to assess the scope and incidence of oral conditions associated with CD relative to the general population. Although hampered by a range in study designs and oral findings that were and were not reported intentionally, the results indicate that indeed CD patients have an increase in oral ulcerations, particularly aphthous ulcers. There was a loose association between the presence of these ulcers and intestinal disease activity. Next, a series of experiments were conducted to identify caspases within the oral cavity and quantify them using three study groups: healthy controls, healthy controls who had localized inflammation around the tooth scheduled for extraction, and patients with biopsy-confirmed CD who were in remission. Histology findings indicated that the CD group had more inflammation in both the lamina propria and epithelial layers compared to the two control groups. Results showed a statistically significant difference in caspase-1 densitometry between CD patients and each set of controls (p˂0.01, for each). The levels of caspase-3 (apoptosis levels) were also detected and quantified to confirm that the inflammatory process in CD patients is more likely to be caspase-1 mediated. CD patients had lower caspase-3 levels in comparison with both control groups (p<0.01, for each). In conclusion, our results provide evidence that caspase-1 is likely to play a critical role in the process of cell death in CD patients. The oral mucosal tissues have similar clinical and immune characteristics of those in the intestinal tract. These findings, although preliminary, suggest that dentists can play a critical role in the diagnosis and monitoring of CD activity in conjunction with gastroenterologists. The oral cavity is readily accessible and mimics key events previously believed to be restricted to intestinal tissues.

• Subjects / Keywords

  • Inflammation
  • Caspase-1
  • Oral
  • Crohn's

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3PN8XP6P

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.