Matos, Carina and Mamilos, Andreas and Shah, Pranali N. and Meedt, Elisabeth and Weber, Daniela and Ghimire, Saroj and Hiergeist, Andreas and Gessner, Andre and Dickinson, Anne and Dressel, Ralf and Walter, Lutz and Stark, Klaus and Heid, Iris M. and Poeck, Hendrik and Edinger, Matthias and Wolff, Daniel and Herr, Wolfgang and Holler, Ernst and Kreutz, Marina and Ghimire, Sakhila (2022) Downregulation of the vitamin D receptor expression during acute gastrointestinal graft versus host disease is associated with poor outcome after allogeneic stem cell transplantation. FRONTIERS IN IMMUNOLOGY, 13: 1028850. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
The vitamin D receptor (VDR) is critical in regulating intestinal homeostasis and emerging evidence demonstrates that VDR deficiency is a critical factor in inflammatory bowel disease pathology. However, no clinical data exist regarding the intestinal expression of VDR in patients after allogeneic haematopoietic stem cell transplantation (HSCT). Analyzing intestinal biopsies from 90 patients undergoing HSCT with mortality follow-up, we demonstrated that patients with severe acute gastrointestinal graft versus host disease (GI-GvHD) showed significant downregulation of VDR gene expression compared to mild or no acute GI-GvHD patients (p = 0.007). Reduced VDR expression was already detectable at acute GI-GvHD onset compared to GvHD-free patients (p = 0.01). These results were confirmed by immunohistochemistry (IHC) where patients with severe acute GI-GvHD showed fewer VDR+ cells (p = 0.03) and a reduced VDR staining score (p = 0.02) as compared to mild or no acute GI-GvHD patients. Accordingly, low VDR gene expression was associated with a higher cumulative incidence of treatment-related mortality (TRM) (p = 1.6x10-6) but not with relapse-related mortality (RRM). A multivariate Cox regression analysis identified low VDR as an independent risk factor for TRM (p = 0.001, hazard ratio 4.14, 95% CI 1.78-9.63). Furthermore, VDR gene expression significantly correlated with anti-microbial peptides (AMPs) gene expression (DEFA5: r = 0.637, p = 7x10-5, DEFA6: r 0 0.546, p = 0.001). In conclusion, our findings suggest an essential role of the VDR in the pathogenesis of gut GvHD and the prognosis of patients undergoing HSCT.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN RECIPIENTS; MARROW; VDR; HSCT; acute GI-GvHD; TRM; defensins |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2023 09:41 |
| Last Modified: | 12 Dec 2023 09:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/57000 |
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