Downregulation of the vitamin D receptor expression during acute gastrointestinal graft versus host disease is associated with poor outcome after allogeneic stem cell transplantation

URN to cite this document:

urn:nbn:de:bvb:355-epub-531216 Copy

DOI to cite this document:

10.5283/epub.53121 Copy

Matos, Carina ; Mamilos, Andreas ; Shah, Pranali N. ; Meedt, Elisabeth ; Weber, Daniela ; Ghimire, Saroj ; Hiergeist, Andreas ; Gessner, André ; Dickinson, Anne M. ; Dressel, Ralf ; Walter, Lutz ; Stark, Klaus J. ; Heid, Iris M. ; Poeck, Hendrik ; Edinger, Matthias ; Wolff, Daniel ; Herr, Wolfgang ; Holler, Ernst ; Kreutz, Marina ; Ghimire, Sakhila

License: Creative Commons Attribution 4.0 PDF - Published Version (4MB)

Date of publication of this fulltext: 31 Oct 2022 08:33

---

Alternative links to fulltext:DOIPublisher

---

Details

Item type:	Article
Journal or Publication Title:	Frontiers in Immunology
Publisher:	Frontiers
Volume:	13
Page Range:	p. 1028850
Date:	20 October 2022
Institutions:	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
Projects:	European Union Grant FP7-PEOPLE-2012-ITN-315963 (CELLEUROPE), Wilhelm Sander Foundation, Grant 2017.020.1, DFG 324392634 - TRR 221, CRC 1371 microbiome signatures, Else Kröner Fresenius Stiftung
Identification Number:	Value Type 10.3389/fimmu.2022.1028850 DOI
Keywords:	VDR, HSCT, acute GI-GvHD, TRM, defensins
Dewey Decimal Classification:	600 Technology > 610 Medical sciences Medicine
Status:	Published
Refereed:	Yes, this version has been refereed
Created at the University of Regensburg:	Yes
Item ID:	53121

Preview

Export bibliographical data

ASCII CitationAtomBibTeXData Cite XMLDataCite XML OAIDublin CoreEndNoteHTML CitationJSON LDMETSMODSOpenAPCRDF+N-TriplesRDF+N3RDF+XMLReferReference ManagerSimple MetadataXMLxMetaDissPlus

---

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 ...

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 (GIGvHD) 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.

---

---

Metadata last modified: 12 Jan 2023 06:16

Owner only: item control page

Download Statistics

Download Statistics

Download Statistics

Download Statistics

Downloads

Downloads per month over past year

Altmetric

Altmetric

Altmetric

Alternative Statistics (altmetrics)

More literature (via CORE)

More literature (via CORE)

More literature (via CORE)

More literature (via CORE)