Abstract
Vitamin D was discovered 100 years ago and since then multiple studies have consistently proved its effect on bone health and mineral metabolism. Further research has also explored its so-called “non-classical” biological effects, encompassing immune regulation and control of cell proliferation and differentiation. Vitamin D downregulates pro-inflammatory immune cells and subsequently their cytokine production, while enhancing the anti-inflammatory subsets, thus mediating inflammation and fostering a more tolerogenic environment. Its biological action is exerted through the vitamin D receptor, a nuclear receptor that mediates gene transcription and is expressed in most cells from the innate and adaptive immunity. Owing to its immune-modulatory properties, its role in cancer pathophysiology, hematology disorders and stem cell transplantation has also been investigated. Vitamin D deficiency causes immune imbalance and cytokine dysregulation, contributing to some autoimmune diseases. In the hematopoietic stem cell transplant setting this could lead to complications such as acute and chronic graft-versus-host disease, ultimately impacting transplant outcomes. Other factors have also been linked to this, including specific polymorphisms of the vitamin D receptor in both stem cell donors and recipients. Nevertheless, studies thus far have shown conflicting results and the use of vitamin D or its receptor as biomarkers has not been validated yet, therefore there are no evidence-based consensus guidelines to guide clinicians in their day-to-day practice. To gain more insight in this topic, we have reviewed the existent literature and gathered the current evidence. This is an overview of the role of serum vitamin D and its receptor as biomarkers for clinical outcomes in patients undergoing hematopoietic stem cell transplantation. Further prospective studies with larger cohorts are warranted to validate the viability of using serum vitamin D, and its receptor, as biomarkers in potential stem cell donors and patients, to identify those at risk of post-transplant complications and enable early therapeutic interventions.
Highlights
Vitamin D has received considerable attention in recent years due to its non-skeletal functions (1, 2), immune regulation (3)
Weak association in patients with lower levels of 25(OH)D3 on day + 100 and Acute GvHD (aGvHD) (P = 0.066) No significant differences in aGvHD 2-years CI of chronic GvHD (cGvHD): 63.8% in VDD patients compared to 23.8% in sufficient VD patients (P = 0.02) Extensive cGvHD at 2-years was 54.5% in VDD patients compared to 14.3% in sufficient VD patients (P = 0.009) NR
Vitamin D is a potent regulator of immune responses with impact in hematopoietic stem cell transplant (HSCT) (9–13)
Summary
Vitamin D has received considerable attention in recent years due to its non-skeletal functions (1, 2), immune regulation (3). Despite controversy in this matter (52, 68), preclinical studies have shown that 1,25(OH)2D3 triggers secretion of IL-10 by CD4+ T cells (69) and TGF-β (transforming growth factor beta) by DCs (55, 57, 67, 70), which enhance the recruitment of Foxp3+ CD25+ regulatory T cells (Treg) (59, 66) These CD4+ lymphocyte subset impairs the expansion of alloreactive donor T cells in GvHD-target tissues and subsequently the synthesis of their pro-inflammatory cytokines, including IL-2 (71). Nearly 50% of lung transplant recipients are vitamin D deficient, as reported by one single center study In this population, low levels of 25(OH)D3 were linked to worse pulmonary function tests and higher graft rejection (111). Three clinical studies have linked 1,25(OH)2D3 serostatus and acute GvHD (aGvHD): Urbain et al demonstrated that patients with moderate to severe aGvHD had lower levels of 25(OH)D3
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