A biomarker panel for acute graft-versus-host disease

Blood. 2009 Jan 8;113(2):273-8. doi: 10.1182/blood-2008-07-167098. Epub 2008 Oct 2.

Abstract

No validated biomarkers exist for acute graft-versus-host disease (GVHD). We screened plasma with antibody microarrays for 120 proteins in a discovery set of 42 patients who underwent transplantation that revealed 8 potential biomarkers for diagnostic of GVHD. We then measured by enzyme-linked immunosorbent assay (ELISA) the levels of these biomarkers in samples from 424 patients who underwent transplantation randomly divided into training (n = 282) and validation (n = 142) sets. Logistic regression analysis of these 8 proteins determined a composite biomarker panel of 4 proteins (interleukin-2-receptor-alpha, tumor-necrosis-factor-receptor-1, interleukin-8, and hepatocyte growth factor) that optimally discriminated patients with and without GVHD. The area under the receiver operating characteristic curve distinguishing these 2 groups in the training set was 0.91 (95% confidence interval, 0.87-0.94) and 0.86 (95% confidence interval, 0.79-0.92) in the validation set. In patients with GVHD, Cox regression analysis revealed that the biomarker panel predicted survival independently of GVHD severity. A panel of 4 biomarkers can confirm the diagnosis of GVHD in patients at onset of clinical symptoms of GVHD and provide prognostic information independent of GVHD severity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / blood*
  • Graft vs Host Disease / mortality
  • Hematopoietic Stem Cell Transplantation*
  • Hepatocyte Growth Factor / blood*
  • Humans
  • Infant
  • Interleukin-2 Receptor alpha Subunit / blood*
  • Interleukin-8 / blood*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Receptors, Tumor Necrosis Factor, Type I / blood*
  • Retrospective Studies
  • Survival Rate
  • Transplantation, Homologous

Substances

  • Biomarkers
  • CXCL8 protein, human
  • HGF protein, human
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-8
  • Receptors, Tumor Necrosis Factor, Type I
  • Hepatocyte Growth Factor