Researchers Identify DKK3 as a Novel Biomarker for Post-Transplant cGVHD

Study findings suggest that an association exists between plasma DKK3 concentrations and nonrelapse mortality in patients with chronic graft-versus-host disease (GVHD; Blood Adv. 2020;4[11]:2409-2417).

Yoshihiro Inamoto, MD, Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan, and colleagues sought to evaluate the link between plasma biomarkers and fibrotic mechanisms of chronic GVHD.

They did this by using multiplex mass spectrometry and pooled samples for biomarker discovery to compare proteomic profiles between patients with newly diagnosed sclerotic chronic GVHD (n = 21), newly diagnosed nonsclerotic chronic GVHD (n = 33), and no chronic GVHD (n = 20).

In addition, Dr Inamoto et al used immunoassay 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: [DKK3 and IL1RAP],” they explained.

According to the analysis was shown to be a biomarker for sclerotic and nonsclerotic chronic GVHD.

Furthermore, in a verification analysis of 186 patients, elevated plasma DKK3 concentrations were tied to chronic GVHD whether or not the patient had sclerosis, and the area under the receiver operating characteristic curve was 0.85 for association between DKK3 concentrations and chronic GVHD.

According to multiple linear regression analysis, chronic GVHD (with or without steroid therapy) and patient age were independently tied to DKK3 concentrations, and the rate of nonrelapse mortality was higher in those with high versus low DKK3 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,” Dr Inamoto and colleagues wrote.

“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,” they concluded.—Hina M. Porcelli