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Published on: March 17, 2020
Association of Plasma CD163 Concentration with De Novo-Onset Chronic Graft-versus-Host Disease
Yoshihiro Inamoto1, Paul J Martin2, Sophie Paczesny3
1Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
Insights
Plasma soluble CD163 levels at day 80 predict de novo chronic graft-versus-host disease (GVHD) risk after transplantation. Higher CD163 indicates increased risk, suggesting macrophage activation or oxidative stress in chronic GVHD pathogenesis.
Area of Science:
- Hematology
- Immunology
- Transplantation Science
Background:
- Chronic graft-versus-host disease (cGVHD) is a major complication following allogeneic hematopoietic cell transplantation.
- Identifying biomarkers for cGVHD risk is crucial for patient management and outcomes.
Purpose of the Study:
- To discover and validate plasma proteins that prognosticate de novo or quiescent-onset chronic GVHD.
- To investigate the role of specific proteins in cGVHD pathogenesis.
Main Methods:
- Proteomic analysis using high-throughput mass spectrometry on pooled plasma samples.
- ELISA validation of candidate proteins in individual patient samples.
- Correlation of protein levels with cGVHD incidence in a discovery and verification cohort.
Main Results:
- Four proteins (LGALS3BP, CD5L, CD163, TXN) were identified as candidates for de novo onset, and two (LGALS3BP, CD5L) for quiescent onset.
- Elevated plasma soluble CD163 concentrations at day 80 were significantly associated with a higher cumulative incidence of de novo-onset cGVHD (75% vs. 40%, P=.018).
- No statistically significant associations were found for other candidate proteins with de novo or quiescent-onset cGVHD.
Conclusions:
- Plasma soluble CD163 is a potential prognostic biomarker for de novo-onset cGVHD.
- Elevated CD163 suggests that monocyte/macrophage activation or increased oxidative stress may play a role in cGVHD development.
Abstract:
Chronic graft-versus-host disease (GVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic cell transplantation. To identify prognostic plasma proteins associated with de novo- or quiescent-onset chronic GVHD (cGVHD), we performed a discovery and validation proteomic study. The total study cohort included 167 consecutive patients who had no clinical evidence of GVHD under minimum glucocorticoid administration and had available plasma samples obtained at 80 ± 14 days after transplantation. We first used high-throughput mass spectrometry to screen pooled plasma using 20 cases with subsequent cGVHD and 20 controls without it, and we identified 20 candidate proteins. We then measured 12 of the 20 candidate proteins by ELISA on the same individual samples and identified 4 proteins for further verification (LGALS3BP, CD5L, CD163, and TXN for de novo onset, and LGALS3BP and CD5L for quiescent onset). The verification cohort included 127 remaining patients. The cumulative incidence of de novo-onset cGVHD was higher in patients with higher plasma soluble CD163 concentrations at day 80 than those with lower concentrations (75% versus 40%, P = .018). The cumulative incidence of de novo- or quiescent-onset cGVHD did not differ statistically according to concentrations of the 3 other proteins at day 80. CD163 is a macrophage scavenger receptor and is elevated in oxidative conditions. These results suggest that monocyte or macrophage activation or increased oxidative stress may contribute to the pathogenesis of cGVHD.
