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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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