title: Proteomic patterns predict acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
abstract: Acute graft-versus-host disease (aGvHD) contributes significantly to morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of GvHD is mainly based on clinical features and tissue biopsies. A noninvasive, unbiased laboratory test for GvHD diagnosis does not exist. Here we describe the application of capillary electrophoresis coupled online with mass spectrometry (CE-MS) to 13 samples from 10 patients with aGvHD of grade II or more and 50 control samples from 23 patients without GvHD. About 170 GvHD-specific polypeptides were detected and a tentatively aGvHD-specific model consisting of 31 polypeptides was chosen, allowing correct classification of 13 of 13 (sensitivity 100.0% [95% confidence interval {CI} 75.1 to 100.0]) aGvHD samples and 49 of 50 (specificity 98.0% [95% CI 89.3 to 99.7]) control samples of the training set. The subsequent blinded evaluation of 599 samples enabled diagnosis of aGvHD greater than grade II, even prior to clinical diagnosis, with a sensitivity of 83.1% (95% CI 73.1 to 87.9) and a specificity of 75.6% (95% CI 71.6 to 79.4). Thus, high-resolution proteome analysis represents an unbiased laboratory-based screening method, enabling diagnosis, and possibly enabling preemptive therapy.
authors.affiliation: Hannover Medical School, Department of Hematology, Hemostasis, and Oncology, Hannover, Germany. mischak-weissinger.eva@mh-hannover.de
authors.forename: Eva M
authors.initials: EM
authors.lastname: Weissinger
authors.forename: Eric
authors.initials: E
authors.lastname: Schiffer
authors.forename: Bernd
authors.initials: B
authors.lastname: Hertenstein
authors.forename: James L
authors.initials: JL
authors.lastname: Ferrara
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.forename: Axel
authors.initials: A
authors.lastname: Zander
authors.forename: Petra
authors.initials: P
authors.lastname: Zürbig
authors.forename: Markus
authors.initials: M
authors.lastname: Kellmann
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000208:Acute Disease; D000818:Animals; D016022:Case-Control Studies; D019075:Electrophoresis, Capillary; D006086:Graft vs Host Disease / Q000175:diagnosis*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D013058:Mass Spectrometry; D010455:Peptides / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D014184:Transplantation, Homologous
chemical_list: D010455:Peptides