A biomarker panel for acute graft-versus-host disease

S Paczesny, OI Krijanovski, TM Braun… - Blood, The Journal …, 2009 - ashpublications.org
S Paczesny, OI Krijanovski, TM Braun, SW Choi, SG Clouthier, R Kuick, DE Misek
Blood, The Journal of the American Society of Hematology, 2009ashpublications.org
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 …
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.
ashpublications.org