Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host-disease after allogeneic stem cell transplantation

Weissinger, E.M. et al. (2013) Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host-disease after allogeneic stem cell transplantation. Leukemia, (doi: 10.1038/leu.2013.210)

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Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one curative treatment for hematologic malignancies, but is compromised by life threatening complications, such as severe acute graft-versus-host disease (aGvHD). Prediction of severe aGvHD as early as possible is crucial to allow timely initiation of treatment. Here we report on a multicentre validation of an aGvHD-specific urinary proteomic classifier (aGvHD_MS17) in 423 patients. Samples (n=1106) were collected prospectively between day +7 and day +130 and analyzed using capillary electrophoresis coupled on-line to mass spectrometry (CE-MS). Integration of aGvHD_MS17 analysis with demographic and clinical variables using a logistic regression model led to correct classification of patients developing severe aGvHD 14 days prior to any clinical signs with 82.4% sensitivity and 77.3% specificity. Multivariate regression analysis showed that aGvHD_MS17 positivity was the only strong predictor for aGvHD grade III or IV (P<0.0001). The classifier consists of 17 peptides derived from albumin, β2-microglobulin, CD99, fibronectin, and various collagen α chains, indicating inssflammation, activation of T-cells, and changes in the extracellular matrix as early signs of GvHD-induced organ damage. This study is currently the largest demonstration of accurate and investigator-independent prediction of patients at risk for severe aGvHD, thus allowing preemptive therapy based on proteomic profiling.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mullen, Dr Bill and Mischak, Professor Harald
Authors: Weissinger, E.M., Metzger, J., Dobbelstein, C., Wolff, D., Schleuning, M., Kuzmina, Z., Greinix, H., Dickinson, A.M., Mullen, W., Kreipe, H., Hamwi, I., Morgan, M., Krons, A., Tchebotarenko, I., Ihlenburg-Schwarz, D., Dammann, E., Collin, M., Ehrlich, S., Diedrich, H., Stadler, M., Eder, M., Holler, E., Mischak, H., Krauter, J., and Ganser, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Leukemia
ISSN:0887-6924
ISSN (Online):1476-5551

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