The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation

Autor: Hans-Heinrich Kreipe, Jochen Metzger, Helmut Diedrich, Lothar Hambach, Hildegard T. Greinix, Christin Human, William Mullen, Anne M. Dickinson, Matthias Schiemann, Patrick Schweier, Jürgen Krauter, A Durban, D Wolf, Arnold Ganser, Gernot Beutel, Irina Türüchanow, O Böhm, Christian Könecke, Julia Raad, Michael Stadler, Eva M. Weissinger, Ernst Holler, Danny Jonigk, D Ihlenburg-Schwarz, Zoya Kuzmina
Rok vydání: 2016
Předmět:
Zdroj: Leukemia. 31(3)
ISSN: 1476-5551
Popis: 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.
Databáze: OpenAIRE