A biomarker panel for acute graft-versus-host disease

Sophie Paczesny, Oleg I. Krijanovski, Thomas M. Braun, Sung W. Choi, Shawn G. Clouthier, Rork Kuick, David E. Misek, Kenneth R. Cooke, Carrie L. Kitko, Angela Weyand, Daniel Bickley, Dawn Jones, Joel Whitfield, Pavan Reddy, John E. Levine, Samir M. Hanash, James L M Ferrara

Research output: Contribution to journalArticle

244 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)273-278
Number of pages6
JournalBlood
Volume113
Issue number2
DOIs
StatePublished - Jan 8 2009
Externally publishedYes

Fingerprint

Biomarkers
Graft vs Host Disease
Grafts
Regression analysis
Transplantation
Regression Analysis
Interleukin-2 Receptor alpha Subunit
Confidence Intervals
Protein Array Analysis
Immunosorbents
Proteins
Hepatocyte Growth Factor
Tumor Necrosis Factor Receptors
Microarrays
Interleukin-8
ROC Curve
Logistics
Assays
Logistic Models
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Paczesny, S., Krijanovski, O. I., Braun, T. M., Choi, S. W., Clouthier, S. G., Kuick, R., ... Ferrara, J. L. M. (2009). A biomarker panel for acute graft-versus-host disease. Blood, 113(2), 273-278. https://doi.org/10.1182/blood-2008-07-167098

A biomarker panel for acute graft-versus-host disease. / Paczesny, Sophie; Krijanovski, Oleg I.; Braun, Thomas M.; Choi, Sung W.; Clouthier, Shawn G.; Kuick, Rork; Misek, David E.; Cooke, Kenneth R.; Kitko, Carrie L.; Weyand, Angela; Bickley, Daniel; Jones, Dawn; Whitfield, Joel; Reddy, Pavan; Levine, John E.; Hanash, Samir M.; Ferrara, James L M.

In: Blood, Vol. 113, No. 2, 08.01.2009, p. 273-278.

Research output: Contribution to journalArticle

Paczesny, S, Krijanovski, OI, Braun, TM, Choi, SW, Clouthier, SG, Kuick, R, Misek, DE, Cooke, KR, Kitko, CL, Weyand, A, Bickley, D, Jones, D, Whitfield, J, Reddy, P, Levine, JE, Hanash, SM & Ferrara, JLM 2009, 'A biomarker panel for acute graft-versus-host disease', Blood, vol. 113, no. 2, pp. 273-278. https://doi.org/10.1182/blood-2008-07-167098
Paczesny S, Krijanovski OI, Braun TM, Choi SW, Clouthier SG, Kuick R et al. A biomarker panel for acute graft-versus-host disease. Blood. 2009 Jan 8;113(2):273-278. https://doi.org/10.1182/blood-2008-07-167098
Paczesny, Sophie ; Krijanovski, Oleg I. ; Braun, Thomas M. ; Choi, Sung W. ; Clouthier, Shawn G. ; Kuick, Rork ; Misek, David E. ; Cooke, Kenneth R. ; Kitko, Carrie L. ; Weyand, Angela ; Bickley, Daniel ; Jones, Dawn ; Whitfield, Joel ; Reddy, Pavan ; Levine, John E. ; Hanash, Samir M. ; Ferrara, James L M. / A biomarker panel for acute graft-versus-host disease. In: Blood. 2009 ; Vol. 113, No. 2. pp. 273-278.
@article{daaf5a61370e4fa1b720bcbe37a367bd,
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.",
author = "Sophie Paczesny and Krijanovski, {Oleg I.} and Braun, {Thomas M.} and Choi, {Sung W.} and Clouthier, {Shawn G.} and Rork Kuick and Misek, {David E.} and Cooke, {Kenneth R.} and Kitko, {Carrie L.} and Angela Weyand and Daniel Bickley and Dawn Jones and Joel Whitfield and Pavan Reddy and Levine, {John E.} and Hanash, {Samir M.} and Ferrara, {James L M}",
year = "2009",
month = "1",
day = "8",
doi = "10.1182/blood-2008-07-167098",
language = "English (US)",
volume = "113",
pages = "273--278",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - A biomarker panel for acute graft-versus-host disease

AU - Paczesny, Sophie

AU - Krijanovski, Oleg I.

AU - Braun, Thomas M.

AU - Choi, Sung W.

AU - Clouthier, Shawn G.

AU - Kuick, Rork

AU - Misek, David E.

AU - Cooke, Kenneth R.

AU - Kitko, Carrie L.

AU - Weyand, Angela

AU - Bickley, Daniel

AU - Jones, Dawn

AU - Whitfield, Joel

AU - Reddy, Pavan

AU - Levine, John E.

AU - Hanash, Samir M.

AU - Ferrara, James L M

PY - 2009/1/8

Y1 - 2009/1/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=58849144772&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58849144772&partnerID=8YFLogxK

U2 - 10.1182/blood-2008-07-167098

DO - 10.1182/blood-2008-07-167098

M3 - Article

C2 - 18832652

AN - SCOPUS:58849144772

VL - 113

SP - 273

EP - 278

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -