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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4403-4412. Prepublished online as a Blood First Edition Paper on February 6, 2008; DOI 10.1182/blood-2007-06-097287.
Submitted June 22, 2007
Department of Biomedical Engineering, Sapporo Medical University, Sapporo, Japan * Corresponding author; email: kokai{at}sapmed.ac.jp.
Although graft-versus-host disease (GVHD) is a life- threatening complication of hematopoietic stem cell transplantation (HSCT), its current diagnosis mainly depends on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate early and accurate recognition of this grave condition. Using proteomics, we screened for plasma proteins specific for GVHD in a mouse model. One peak with 8,972 m/z retained a discriminatory value in two diagnostic groups (GVHD and normal controls) with increased expression in the disease, decreased expression during cyclosporin A treatment and was barely detectable in syngeneic transplantation. Purification and mass analysis identified this molecule as CCL8, a member of a large chemokine family. In human samples, the serum concentration of CCL8 correlated closely with GVHD severity. All non-GVHD samples contained less than 48 pg/mL (mean+/-SE: 22.5+/-5.5, range: 12.6-48.0 pg/mL, n=7). In sharp contrast, CCL8 was highly upregulated in GVHD sera ranging from 52.0 to 333.6 pg/mL (mean+/-SE: 165.0 +/-39.8 pg/mL, n=7). Strikingly, two patients with severe fatal GVHD had extremely high levels of CCL8, i.e. 333.6 and 290.4 pg/mL. CCL8 is a promising specific serum marker for the early and accurate diagnosis of GVHD.
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