Dickkopf-related protein 3 is a novel biomarker for chronic GVHD after allogeneic hematopoietic cell transplantation
Open Access
- 9 June 2020
- journal article
- research article
- Published by American Society of Hematology in Blood Advances
- Vol. 4 (11), 2409-2417
- https://doi.org/10.1182/bloodadvances.2020001485
Abstract
To identify plasma biomarkers associated with fibrotic mechanisms of chronic graft-versus-host disease (GVHD), we used multiplex mass spectrometry with pooled samples for biomarker discovery in comparing proteomic profiles between patients with newly diagnosed sclerotic chronic GVHD (n = 21), those with newly diagnosed nonsclerotic chronic GVHD (n = 33), and those without chronic GVHD (n = 20). Immunoassay was used to measure protein concentrations of individual discovery samples and 186 independent verification samples. The discovery mass spectrometry analysis identified 2 candidate proteins with at least 1.5-fold difference in sclerotic GVHD: Dickkopf-related protein 3 (DKK3) and interleukin-1 receptor accessory protein (IL1RAP). Analysis of individual discovery samples by immunoassay showed that DKK3, a modulator of the Wnt signaling pathway, was a biomarker for both sclerotic and nonsclerotic chronic GVHD. Verification analysis of 186 patients confirmed that elevated plasma DKK3 concentrations were associated with chronic GVHD, regardless of the presence or absence of sclerosis, and that the area under the receiver operating characteristic curve was 0.85 for association of DKK3 concentrations with chronic GVHD. Multiple linear regression analysis showed that chronic GVHD with or without steroid treatment and patient age were independently associated with DKK3 concentrations. Patients with high DKK3 concentrations had a higher nonrelapse mortality than those with low concentrations. The lower IL1RAP concentrations in patients with sclerotic GVHD compared with other conditions in the discovery cohort were not confirmed in the verification cohort. DKK3 is a novel biomarker for chronic GVHD. Further studies are needed to determine the biological functions of DKK3 in the pathogenesis of chronic GVHD.This publication has 32 references indexed in Scilit:
- Plasma CXCL9 elevations correlate with chronic GVHD diagnosisBlood, 2014
- A Novel Soluble Form of Tim-3 Associated with Severe Graft-versus-Host DiseaseTransplantation and Cellular Therapy, 2013
- Incidence, risk factors, and outcomes of sclerosis in patients with chronic graft-versus-host diseaseBlood, 2013
- Systemic effects of Wnt signalingJournal of Cellular Physiology, 2013
- Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of diseaseBlood, 2011
- Rationale and Design of the Chronic GVHD Cohort Study: Improving Outcomes Assessment in Chronic GVHDTransplantation and Cellular Therapy, 2011
- Bronchiolitis Obliterans After Allogeneic Hematopoietic Stem Cell TransplantationJAMA, 2009
- Reduced-Intensity Conditioning Regimen Workshop: Defining the Dose Spectrum. Report of a Workshop Convened by the Center for International Blood and Marrow Transplant ResearchTransplantation and Cellular Therapy, 2009
- High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host DiseaseClinical Cancer Research, 2007
- Chronic graft-versus-host diseaseTransplantation and Cellular Therapy, 2003