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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.
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TRANSPLANTATION
Proteomic patterns predict acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Eva M. Weissinger1,
Eric Schiffer2,
Bernd Hertenstein1,3,
James L. Ferrara4,
Ernst Holler5,
Michael Stadler1,
Hans-Jochem Kolb6,
Axel Zander7,
Petra Zürbig2,
Markus Kellmann8, and
Arnold Ganser1
1 Hannover Medical School, Department of Hematology, Hemostasis, and Oncology, Hannover, Germany;
2 Mosaiques-Diagnostics and Therapeutics AG, Hannover Germany;
3 Klinikum Bremen Mitte GmbH, Innere Medizin I, Bremen, Germany;
4 Department of Pediatrics and Internal Medicine, University of Michigan Medical School, Ann Arbor, MI;
5 University of Regensburg, Department of Hematology, Bone Marrow Transplantation Unit, Regensburg, Germany;
6 Clinical Cooperative Group for Hematopoietic Stem Cell Transplantation, Department of Medicine III, Ludwig-Maximilians-University, Munich, Germany;
7 University Clinic Hamburg-Eppendorf, Bone Marrow Transplant Unit, Hamburg, Germany;
8 Thermo Electron, Bremen, Germany
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 noninvasive, 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 of grade II or more 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 of 13 (sensitivity 100.0% [95% confidence interval {CI} 75.1 to 100.0]) aGvHD samples and 49 of 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 greater than 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, and possibly enabling preemptive therapy.
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