Abstract
Objectives
Allogeneic hematopoietic cell transplantation (HCT) is associated with acute graft-vs.-host disease (aGVHD). The presented study applied a novel multiplex antibody-based proximity extension assay (PEA) proteomic platform that can detect thousands of serum proteins simultaneously for the identification of potential biomarkers of aGVHD.
Methods
Serum samples from 28 patients who underwent allogeneic HCT for acute myeloid leukemia (AML) were analyzed; 17 were diagnosed with grade II–IV aGVHD while 11 patients were not. Samples collected on day −6, day 0, +14, +30, +60 and +90 post-HCT were analyzed for the relative concentrations of 552 proteins. The concentration of each protein from baseline to the closest time point before onset of aGVHD, or to the latest time point in control patients, was documented.
Results
Individualized analysis identified 26 proteins demonstrating ≥3-fold increase at aGVHD onset compared to baseline, eliminating proteins with a similar increase in controls. Another approach used paired t-testing and logistic regression that identified a four-marker panel, including SLAMF7, IL-1ra, BTN3A2 and DAB2, where individual log-likelihood ratios ranged from 3.99 to 8.15 (logistic regression, p=0.004–0.046). When combined, the four-marker panel demonstrated an area under the curve (AUC) of 0.90 (95% CI: 0.78–1.00; p=0.0006) with high negative predictive value of 81.8% and positive predictive value of 86.7%. All four markers play a physiological role in immune regulation. Among these, three were also present in the individualized analysis (SLAMF7, IL-1ra and BTN3A2).
Conclusions
We conclude that serum proteins identified using multiplex proteomics, particularly SLAMF7, IL-1ra, BTN3A2 and DAB2, may potentially predict aGVHD.
Funding source: Friends for life fund, Princess Margaret Foundation
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Research funding: Funding sources for this study include the Friends for Life Fund, Princess Margaret Foundation.
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Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: This study was approved by the Institutional Review Board.
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Disclosures: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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