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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5511-5519.
Prepublished online as a Blood First Edition Paper on March 5, 2007; DOI 10.1182/blood-2007-01-069757.
 Previous Article | Next Article 
Submitted January 24, 2007
Accepted February 27, 2007
Proteomic patterns predict acute graft-versus-host
disease after allogeneic hematopoietic stem cell
transplantation
Eva M Weissinger*, Eric Schiffer, Bernd Hertenstein, James L Ferrara, Ernst Holler, Michael Stadler, Hans-Jochem Kolb, Axel Zander, Petra Zurbig, Markus Kellmann, and Arnold Ganser
Dept of Hematology, Hemostasis, Oncology, Hannover Medical School, Hannover, Germany
Mosaiques-diagnostics & therapeutics AG, Hannover, Germany
Hamatologie, Klinikum Bremen Mitte GmbH, Innere Medizin I, Bremen, Germany
Dept of Pediatrics and Internal Medicine, University of Michigan Medical School, Ann Abor, MI, United States
Dept of Hematology, Bone Marrow Transplantation Unit, University of Regensburg, Regensburg, Germany
Dept Med III, Clinical cooperative group for hematopoietic stem cell transplantation, Ludwig-Maximilians-Univ, Munich, Germany
Bone Marrow Transplantation Unit, University Clinic Hamburg-Eppendorf, Hamburg, Germany
Thermo Electron Corporations, Bremen, Germany
* Corresponding author; email: mischak-weissinger.eva{at}mh-hannover.de.
Acute graft versus host disease (aGvHD) contributes significantly to morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of GvHD is mainly based on clinical features and tissue biopsies. A non-invasive, unbiased laboratory test for GvHD diagnosis does not exist. Here we describe the application of capillary electrophoresis coupled online with mass spectrometry (CE-MS) to 13 samples from 10 patients with aGvHD > grade II and 50 control samples from 23 patients without GvHD. About 170 GvHD-specific polypeptides were detected and a tentatively aGvHD-specific model consisting of 31 polypeptides was chosen, allowing correct classification of 13/13 (sensitivity 100.0 % [95 % CI 75.1 to 100.0]) aGvHD samples and 49/50 (specificity 98.0 % [95 % CI 89.3 to 99.7]) control samples of the training set. The subsequent blinded evaluation of 599 samples enabled diagnosis of aGvHD > grade II, even prior to clinical diagnosis with a sensitivity of 83.1% [95% CI 73.1 to 87.9]) and a specificity of 75.6 % [95% CI 71.6 to 79.4]. Thus, high resolution proteome analysis represents an unbiased laboratory based screening method, enabling diagnosis, possibly enabling pre-emptive therapy.
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