title: A biomarker panel for acute graft-versus-host disease.
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.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, USA. sophiep@umich.edu
authors.forename: Sophie
authors.initials: S
authors.lastname: Paczesny
authors.forename: Oleg I
authors.initials: OI
authors.lastname: Krijanovski
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
authors.forename: Sung W
authors.initials: SW
authors.lastname: Choi
authors.forename: Shawn G
authors.initials: SG
authors.lastname: Clouthier
authors.forename: Rork
authors.initials: R
authors.lastname: Kuick
authors.forename: David E
authors.initials: DE
authors.lastname: Misek
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Kitko
authors.forename: Angela
authors.initials: A
authors.lastname: Weyand
authors.forename: Daniel
authors.initials: D
authors.lastname: Bickley
authors.forename: Dawn
authors.initials: D
authors.lastname: Jones
authors.forename: Joel
authors.initials: J
authors.lastname: Whitfield
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
authors.forename: Samir M
authors.initials: SM
authors.lastname: Hanash
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007223:Infant; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; C066855:HGF protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D016209:Interleukin-8; D047888:Receptors, Tumor Necrosis Factor, Type I; D017228:Hepatocyte Growth Factor