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Blood, 8 January 2009, Vol. 113, No. 2, pp. 273-278. Prepublished online as a Blood First Edition Paper on October 2, 2008; DOI 10.1182/blood-2008-07-167098.
Submitted July 8, 2008
Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States * Corresponding author; email: sophiep{at}umich.edu.
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 transplant patients that revealed eight potential biomarkers for diagnostic of GVHD. We then measured by ELISA the levels of these biomarkers in samples from 424 transplant patients randomly divided into training (n = 282) and validation (n = 142) sets. Logistic regression analysis of these eight proteins determined a composite biomarker panel of four 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 two 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 four biomarkers can confirm the diagnosis of GVHD in patients at onset of clinical symptoms of GVHD and provide prognostic information independent of GVHD severity.
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