title: Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host disease after allogeneic stem cell transplantation.
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 peptides derived from albumin, β2-microglobulin, CD99, fibronectin and various collagen α-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.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: E M
authors.initials: EM
authors.lastname: Weissinger
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Metzger
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Dobbelstein
authors.affiliation: Deptartment of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Wolff
authors.affiliation: Deutsche Klinik für Diagnostik, Wiesbaden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schleuning
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Z
authors.initials: Z
authors.lastname: Kuzmina
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Greinix
authors.affiliation: Department of Hematology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Dickinson
authors.affiliation: Biomarkers and Systems Medicine group, University of Glasgow, Glasgow, UK.
authors.forename: W
authors.initials: W
authors.lastname: Mullen
authors.affiliation: Department of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kreipe
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Hamwi
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Krons
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Tchebotarenko
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Ihlenburg-Schwarz
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Dammann
authors.affiliation: Department of Hematology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
authors.forename: M
authors.initials: M
authors.lastname: Collin
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Diedrich
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stadler
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Eder
authors.affiliation: Deptartment of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krauter
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Laboratory of Transplantation Biology, Hannover Medical School, Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000652:urine; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D012709:Serum Albumin / Q000032:analysis; D014184:Transplantation, Homologous
chemical_list: D012709:Serum Albumin