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Lookup NU author(s): Professor Anne Dickinson
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© 2017 Macmillan Publishers Limited, part of Springer Nature. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD-MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD-MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD-MS14 classification. Sensitivity further increased to 93% by combination of cGvHD-MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD-MS14. cGvHD-MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin β-4, eukaryotic translation initiation factor 4γ2, fibrinogen β-chain or collagens. In conclusion, the cGvHD-MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention.
Author(s): Weissinger EM, Human C, Metzger J, Hambach L, Wolf D, Greinix HT, Dickinson AM, Mullen W, Jonigk D, Kuzmina Z, Kreipe H, Schweier P, Bohm O, Turuchanow I, Ihlenburg-Schwarz D, Raad J, Durban A, Schiemann M, Konecke C, Diedrich H, Holler E, Beutel G, Krauter J, Ganser A, Stadler M
Publication type: Article
Publication status: Published
Print publication date: 01/03/2017
Online publication date: 04/11/2016
Acceptance date: 30/08/2016
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
Publisher: Nature Publishing Group
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