According to a report in Frontiers in Immunology, nascent data suggest that vitamin D receptor (VDR) deficiency is a major factor in inflammatory bowel disease pathology. The report’s authors also noted, however, that no evidence on intestinal expression of VDR after allogeneic hematopoietic cell transplantation (HCT) has been presented.
Based on analyses of intestinal biopsies, researchers revealed what appeared to be an “essential role” of VDR gene expression in the pathology of gastrointestinal graft-versus-host disease (GI-GVHD), as well as the prognosis of recipients of HCT.
Vitamin D Receptor Deficiency Drives GI-GVHD
The study included gastrointestinal biopsies from 90 adult patients (small intestine, 33; large intestine, 57) who underwent HCT between October 2009 and November 2013. At the time of collection, 57 patients showed no symptoms of gut GVHD (median days after HCT, 62), 24 patients showed symptoms suggestive of GVHD onset (median days after HCT, 78), and 9 patients had persistent or recurrent acute GVHD (median days after HCT, 175).
Patients with severe acute GI-GVHD had significant downregulation of VDR gene expression compared with patients with mild or no acute GVHD (P=.007). In addition, VDR downregulation was observed at the onset of acute GVHD compared with patients without GVHD (P=.01). Via immunohistochemistry, the authors also found reduced VDR+ cells (P=.03) and VDR staining scores (P=.02) in patients with severe acute GI-GVHD relative to patients with mild or no GVHD, reaffirming their VDR findings.
Of note, low gene expression of VDR was associated with a greater cumulative incidence of treatment-related mortality (P=.0000016), but not relapse-related mortality. Cox regression models found a 4-fold increased risk for treatment-related mortality in patients with low VDR (hazard ratio, 4.14; 95% CI, 1.78-9.63; P=.001).
“In this study, we present clinical evidence suggesting that the VDR plays a critical and multifaceted role in acute GI-GVHD and mortality,” the authors summarized. They added that high-dose vitamin D3 supplementation could be a potential rescue therapy for patients with low VDR.