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

Weissinger, E.M. et al. (2017) The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation. Leukemia, 31(3), pp. 654-662. (doi: 10.1038/leu.2016.259) (PMID:27677743)

Abstract

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.

• Item Type: Articles
• Additional Information: The work was supported in part by grants provided by the German José-Carreras-Leukemia-Foundation (DJCS) R11/09 to DW and EMW; PS was sponsored by DJCLS; The German Research foundation (EMW and AG): CH and DI-S were supported by SFB738-project A02 and the ITN Project Celleurope (315963) to AMD. We thank Mohamed Dakna for excellent help with the statistical analyses and Dipl Dok Elke Dammann for excellent assistance with clinical data bases. Grants: Stem diagnostics (AMD, Harald Mischak (WP4)); SFB738 (EMW, AG), project A02; Deutsche-Jose-Carreras Leukämie-Stiftung (DJCLS) (DW, EMW) Celleurope 315963 (AMD).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mullen, Dr Bill
• Authors: Weissinger, E.M., Human, C., Metzger, J., Hambach, L., Wolf, D., Greinix, H.T., Dickinson, A.M., Mullen, W., Jonigk, D., Kuzmina, Z., Kreipe, H., Schweier, P., Böhm, O., Türüchanow, I., Ihlenburg-Schwarz, D., Raad, J., Durban, A., Schiemann, M., Könecke, C., Diedrich, H., Holler, E., Beutel, G., Krauter, J., Ganser, A., and Stadler, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Leukemia
• Publisher: Nature Publishing Group
• ISSN: 0887-6924
• ISSN (Online): 1476-5551
• Published Online: 04 November 2016