Cellular and molecular mechanisms in the pathogenesis of irritable bowel syndrome
Author: Mohammadian Kermani, Ghazaleh
Date: 2023-11-24
Location: Birkeaulan 2, F52, Karolinska University Hospital, Huddinge
Time: 13:00
Department: Inst för medicin, Huddinge / Dept of Medicine, Huddinge
View/ Open:
Thesis (1.042Mb)
Abstract
Irritable bowel syndrome (IBS) is part of the functional bowel disorder spectrum
with no single accepted theory of its development and no biological marker for
diagnosis. Today the diagnosis is defined by the ROME criteria, but this is not
always correlated to the diagnosis the clinician gives. It has been difficult to find
a single biomarker for IBS due to many reasons. One is the heterogeneity of IBS
since it may include conditions that really are not IBS. Some conditions, that
have been a part of IBS spectrum, have now its own disease entity, for example,
enteric dysmotility or bile acid diarrhea. Another reason for difficulty in finding
biomarkers is the morphometry method used to analyze mucosal cells. Most
studies have focused on counting cells per high-power field, and this could be
difficult if the mucosa that is chosen has an uneven stretch or if there is a highpower field without presence of mucosa. We therefore wanted to investigate if
the method of counting cells per region of interest would be a more objective
and applicable method in identifying patients with IBS. The general aim of this
project was to identify cellular and molecular markers in patients with IBS.
Another aim was to find histopathological changes that could explain the
etiology of IBS. The cells that have been analyzed are mast cells and
enteroendocrine cells. We have also analyzed the expression of human betadefensin 2.
In study I, we analyzed enteroendocrine cells expressing serotonin and chromogranin A in jejunum of patients with IBS and healthy volunteers. We analyzed the morphometry with two different methods, one analyzing per highpower field, and one analyzing per mm2 . There was no difference in the number of EEC between patients and healthy volunteers, but the conclusion from the study was that counting per mm2 is a more objective method for morphometry.
In study II, the colonic mucosa was stained for human beta-defensin 2 (HBD2) and patients with IBS had lower expression of HBD2 compared to patients with inflammatory bowel disease and healthy volunteers, that might indicate that HBD2 have role in the pathogenesis of IBS.
In study III, mast cells expressing tryptase and CD117 in jejunum of patients with IBS were analyzed and compared to healthy volunteers. There were a lower number of tryptase positive cells in patients with IBS-D compared to healthy volunteers and a decrease of intraepithelial CD117 mast cells in patients with IBS compared to healthy controls, latest a novel finding. In conclusion, mast cells might have a role in the pathogenesis of IBS and that more focus should be on the intraepithelial mast cells in future studies.
In study I, we analyzed enteroendocrine cells expressing serotonin and chromogranin A in jejunum of patients with IBS and healthy volunteers. We analyzed the morphometry with two different methods, one analyzing per highpower field, and one analyzing per mm2 . There was no difference in the number of EEC between patients and healthy volunteers, but the conclusion from the study was that counting per mm2 is a more objective method for morphometry.
In study II, the colonic mucosa was stained for human beta-defensin 2 (HBD2) and patients with IBS had lower expression of HBD2 compared to patients with inflammatory bowel disease and healthy volunteers, that might indicate that HBD2 have role in the pathogenesis of IBS.
In study III, mast cells expressing tryptase and CD117 in jejunum of patients with IBS were analyzed and compared to healthy volunteers. There were a lower number of tryptase positive cells in patients with IBS-D compared to healthy volunteers and a decrease of intraepithelial CD117 mast cells in patients with IBS compared to healthy controls, latest a novel finding. In conclusion, mast cells might have a role in the pathogenesis of IBS and that more focus should be on the intraepithelial mast cells in future studies.
List of papers:
I. Mohammadian G, Dlugosz A, Shetye J, Lindberg G. Quantification of mucosal EEC in jejunum. A comparative study of IBS patients and healthy control. Scand J of Gastroenterology. 2020, VOL. 55, NO. 5, 543–548.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Mohammadian G, Dlugosz A, Lindberg G. Human b-defensins in colonic mucosa of patients with irritable bowel syndrome, inflammatory bowel disease and healthy controls - A pilot study. Annals of Gastroenterology, Liver and pancreatic diseases. 2023 Jan. 3:1-9.
III. Mohammadian G, Dlugosz A, Shariat A, Shetye J, Lindberg G. Mast cells in jejunum of patients with IBS. [Manuscript]
I. Mohammadian G, Dlugosz A, Shetye J, Lindberg G. Quantification of mucosal EEC in jejunum. A comparative study of IBS patients and healthy control. Scand J of Gastroenterology. 2020, VOL. 55, NO. 5, 543–548.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Mohammadian G, Dlugosz A, Lindberg G. Human b-defensins in colonic mucosa of patients with irritable bowel syndrome, inflammatory bowel disease and healthy controls - A pilot study. Annals of Gastroenterology, Liver and pancreatic diseases. 2023 Jan. 3:1-9.
III. Mohammadian G, Dlugosz A, Shariat A, Shetye J, Lindberg G. Mast cells in jejunum of patients with IBS. [Manuscript]
Institution: Karolinska Institutet
Supervisor: Lindberg, Greger
Co-supervisor: Dlugosz, Aldona; Shetye, Jayant
Issue date: 2023-10-23
Rights:
Publication year: 2023
ISBN: 978-91-8017-172-4
Statistics
Total Visits
Views | |
---|---|
Cellular ... | 233 |
Total Visits Per Month
December 2023 | January 2024 | February 2024 | March 2024 | April 2024 | May 2024 | June 2024 | |
---|---|---|---|---|---|---|---|
Cellular ... | 12 | 14 | 12 | 20 | 10 | 12 | 13 |
File Visits
Views | |
---|---|
Thesis_Ghazaleh_Mohammadian_Kermani.pdf | 156 |
Top country views
Views | |
---|---|
Sweden | 42 |
United States | 42 |
Australia | 5 |
Bulgaria | 5 |
China | 5 |
Ireland | 5 |
India | 5 |
Russia | 5 |
Germany | 4 |
Greece | 4 |
Top cities views
Views | |
---|---|
Gävle | 9 |
Stockholm | 7 |
Farsta strand | 4 |
Wembley | 4 |
Ashburn | 3 |
Bellevue | 3 |
Los Angeles | 3 |
Seattle | 3 |
Stara Zagora | 3 |
Zurich | 3 |