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

Abstract

Chronic graft-versus-host disease (cGVHD) is the leading cause of long-term morbidity and mortality after allogeneic hematopoietic cell transplantation. In order to identify prognostic plasma proteins associated with de novo or quiescent-onset 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 identified 20 candidate proteins. We then measured 12 of the 20 candidates by enzyme-linked immunosorbent assays 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=0.018). The cumulative incidence of de novo or quiescent-onset cGVHD did not differ statistically according to concentrations of the three 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.

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

“…For this reason, it is important that we establish clinical laboratory parameters that can be used to follow the response to ECP. In the past 5 years, several biomarkers emerged as useful predictors of chronic GvHD onset, severity, and therapy refractoriness; notably, suppression of tumorigenicity 2 (ST2), matrix metalloproteinase‐3 (MMP3), chemokine (C‐X‐C motif) ligand 9 (CXCL9), CXCL10, CXCL11, CD163, and B‐cell activating factor (BAFF) . In an effort to explore previously established chronic GvHD biomarkers in the context of ECP, we conducted a proof‐of‐principle study wherein clinical characteristics were systematically captured and serum was collected before ECP and at 2‐month intervals for 6 months for the purpose of biomarker testing.…”

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease

“…CD163 is a macrophage scavenger receptor elevated in oxidative conditions [52]. 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.…”

“…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. The group suggested that monocyte or macrophage activation or increased oxidative stress may contribute to the pathogenesis of cGVHD [52]. …”

Clinical Proteomics for Post‐Hematopoeitic Stem Cell Transplantation Outcomes

“…Altogether, the IFN‐inducible chemokines CXCL9 and CXCL10, responsible for CXCR3 expressing Th1/NK lymphocyte recruitment into tissues, are upregulated at diagnosis and are worth being pursued and tested in prospectively collected samples. Plasma CD163 concentration has been associated with de novo‐onset cGVHD . Using a combination of flow and mass cytometry, it was shown that patients with more severe cGVHD had lower mucosal‐associated T cell frequencies, with a concomitant higher level of CD38 expression on T cells .…”