Weber, Daniela and Frauenschlaeger, Katrin and Ghimire, Sakhila and Peter, Katrin and Panzer, Isabella and Hiergeist, Andreas and Weber, Markus and Kutny, Daniel and Wolff, Daniel and Grube, Matthias and Huber, Elisabeth and Oefner, Peter and Gessner, Andre and Hehlgans, Thomas and Herr, Wolfgang and Holler, Ernst (2017) The association between acute graft-versus-host disease and antimicrobial peptide expression in the gastrointestinal tract after allogeneic stem cell transplantation. PLOS ONE, 12 (9): e0185265. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Intestinal microbiota disruption is associated with acute gastrointestinal (GI) Graft-versus-Host Disease (GvHD) and poor outcome after allogeneic stem cell transplantation (ASCT). Here, in a retrospective analysis of 200 patients undergoing ASCT at the Regensburg University Medical Center, we assessed the relative expression of Paneth cell antimicrobial peptides (AMPs), Human Defensins (HD) 5 and 6 and regenerating islet-derived 3 alpha (Reg3 alpha), in 292 human intestinal biopsies as well as Reg3a serum levels in relation to acute GI GvHD. In the absence of GI GvHD, the relative expression of Paneth cell AMPs was significantly higher in the small intestine (duodenum to ileum) than in the stomach and large intestine (cecum to rectum) for Reg3a (p <= 0.001), HD5 (p <= 0.002) and HD6 (p <= 0.02). Acute stage 2-4 GI GvHD was associated with reduced expression of AMPs in the small intestine (p <= 0.01) in comparison to stage 0-1 disease, accompanied by a decrease in Paneth cell count in case of severe acute GI GvHD (p<0.001). The opposite held true for the large intestine as we found stage 2-4 GI GvHD correlated with significantly higher expression of HD5, HD6, and Reg3a compared to mild or no acute GI GvHD (p <= 0.002). Severe GI GvHD in both the lower and the upper GI tract also correlated with higher serum concentrations of Reg3a (p = 0.002). As indirect markers of intestinal microbiome diversity low levels of urinary 3-indoxyl sulfate levels were associated with severe stages of acute GI GvHD compared to mild stage or no acute GI GvHD (p = 0.05). In conclusion, acute GI GvHD correlates with intestinal expression of HD5, HD6 and Reg3a as well as Reg3a serum levels and is associated with intestinal dysbiosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALPHA-DEFENSINS; GVHD; MORTALITY; INTERLEUKIN-22; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Orthopädie Medicine > Lehrstuhl für Pathologie Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:15 |
| Last Modified: | 26 Feb 2019 11:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1168 |
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