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Biol Blood Marrow Transplant. 2017 Aug;23(8):1250-1256. doi: 10.1016/j.bbmt.2017.04.019. Epub 2017 Apr 25.

Association of Plasma CD163 Concentration with De Novo-Onset Chronic Graft-versus-Host Disease.

Author information

1
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. Electronic address: yinamoto@fredhutch.org.
2
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
3
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
4
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
5
Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington.

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.

KEYWORDS:

Biomarker discovery; CD163; Chronic graft-versus-host disease; Macrophage

PMID:
28455006
PMCID:
PMC5511087
DOI:
10.1016/j.bbmt.2017.04.019
[Indexed for MEDLINE]
Free PMC Article

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