Medizinische Universität Graz - Research portal
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SHR Neuro Cancer Cardio Lipid Metab Microb
Robak, O; Kastner, MT; Stecher, C; Schneider, M; Andreas, M; Greinix, H; Kallay, E; Honsig, C; Steininger, C.
Cytomegalovirus Infection Downregulates Vitamin D Receptor in Patients Undergoing Hematopoietic Stem Cell Transplantation
TRANSPLANTATION. 2021; 105(7): 1595-1602.
Doi: 10.1097/TP.0000000000003448
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Andreas Martin
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- Abstract:
- Supplemental Digital Content is available in the text. Background.Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with hematologic diseases but is associated with high mortality and morbidity. Cytomegalovirus (CMV) infection is common in HSCT patients and modulates vitamin D metabolism in vitro. We aimed at validating CMV-associated vitamin D metabolism in vivo in HSCT.Methods.Patients treated for significant CMV viremia after HSCT were evaluated for CMV load before, during, and after antiviral treatment. RNA was isolated from whole-blood samples to test for regulation of key components of the vitamin D receptor (VDR) pathway during different phases of CMV viremia.Results.CMV viremia developed a mean time of 102 (+/- 34) d post-HSCT. Maximum levels of CMV-DNA reached a mean of 5668 (+/- 7257) copies/mL. VDR expression was downregulated to a mean of 64.3% (+/- 42.5%) relative to the VDR expression pre-CMV viremia (P = 0.035) and lagged in recovery following antiviral treatment. Toll-like receptor (TLR) 2 mRNA was upregulated to 225.4% during CMV viremia relative to the expression pre-CMV viremia (P = 0.012) but not TLR6/7/8 and the TLR-adaptor protein MyD88. Levels of 25-OH vitamin D were reduced in all viremic patients (48.0 +/- 4.8 versus 25.1 +/- 3.7 ng/mL) and were even lower after periods of CMV viremia compared with the control group (48.3 +/- 3.5 versus 17.8 +/- 1.8 ng/mL; P = 0.008).Conclusions.CMV viremia is associated with significant dysregulation of vitamin D metabolism in HSCT patients.