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

Lookup NU author(s): Professor Anne Dickinson, Professor Matthew CollinORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Allogeneic hematopoietic stem cell transplantation is one curative treatment for hematological 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. 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 before 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 peptidesderived from albumin, beta 2-microglobulin, CD99, fibronectin and various collagen alpha-chains, indicating inflammation, 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.

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Author(s): Weissinger EM, Metzger J, Dobbelstein C, Wolff D, Schleuning M, Kuzmina Z, Greinix H, Dickinson AM, 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, Ganser A

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2014

Volume: 28

Issue: 4

Pages: 842-852

Print publication date: 01/04/2014

Online publication date: 02/08/2013

Acceptance date: 11/07/2013

Date deposited: 22/08/2014

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/leu.2013.210

DOI: 10.1038/leu.2013.210

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