Year-end Sale % OFF 
Abstract
The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the plasma was comprehensively characterized with respect to its lipidome and metabolome via liquid chromatography/mass spectrometry (LCMS) and gas chromatography/mass spectrometry (GCMS). A pro-inflammatory metabolic profile was observed in patients who eventually developed GVHD. Five potential pre-transplant biomarkers, 2-aminobutyric acid, 1-monopalmitin, diacylglycerols (DG 38:5, DG 38:6), and fatty acid FA 20:1 demonstrated high sensitivity and specificity towards predicting post-transplant GVHD. The resulting predictive model demonstrated an estimated predictive accuracy of risk stratification of 100%, with area under the curve of the ROC of 0.995. The likelihood ratio of 1-monopalmitin (infinity), DG 38:5 (6.0), and DG 38:6 (6.0) also demonstrated that a patient with a positive test result for these biomarkers following conditioning and prior to transplant will be at risk of developing GVHD. Collectively, the data suggest the possibility that pre-transplant metabolic signature may be used for risk stratification of SCT recipients with respect to development of alloreactivity.
Highlights
Transplantation of hematopoietic progenitors from an human leukocyte antigen (HLA)-matched donor is a curative procedure for many patients with hematologic malignancies and disorder of hematopoiesis
We describe the lipidomic and metabolomic profiles of patients undergoing myeloablative conditioning and stem cell transplantation and try to understand the role of these metabolites in mediating alloreactivity, and for potentially predicting graft vs. host disease (GVHD)
Our study demonstrates that the pre-transplant lipidome and the metabolome of stem cell transplantation (SCT) recipients has significant potential towards their risk stratification with respect to the development of GVHD, indicating potential use as biomarkers for this purpose
Summary
Transplantation of hematopoietic progenitors from an HLA-matched donor is a curative procedure for many patients with hematologic malignancies and disorder of hematopoiesis. The T cells encounter these alloantigens, undergo activation, and perform functions such as cytokine secretion (IL-2, IL-4, IL-10, IL-12, IL-17, and interferon gamma by helper T cell subsets) and target lysis (granzyme and perforin secretion by cytotoxic T cells) These functions are accompanied by significant metabolic adaptations in the T cells, including increased glycolysis and oxygen consumption as well as cytokine production [1]. Correlation has been shown between intracellular ATP concentration in T cells and severity of clinical GVHD in humans, and between increasing glycolysis and GVHD in murine models [3,4] These observations suggest that donor T cell activation and consequent metabolic and biosynthetic changes may correlate with clinical events as immune reconstitution occurs following SCT, and alloreactivity is triggered
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
