The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation.
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.
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
E M
EM
Weissinger
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
C
C
Human
Mosaiques-Diagnostics, Hannover, Germany.
J
J
Metzger
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
L
L
Hambach
Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
D
D
Wolf
1st Department of Internal Medicine, Medical University of Vienna, Vienna, Austria and Division of Hematology, Medical University of Graz, Graz, Austria.
H T
HT
Greinix
Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
A M
AM
Dickinson
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
W
W
Mullen
Institute of Pathology, Hannover Medical School, Hannover, Germany.
D
D
Jonigk
1st Department of Internal Medicine, Medical University of Vienna, Vienna, Austria and Division of Hematology, Medical University of Graz, Graz, Austria.
Z
Z
Kuzmina
Institute of Pathology, Hannover Medical School, Hannover, Germany.
H
H
Kreipe
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
P
P
Schweier
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
O
O
Böhm
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
I
I
Türüchanow
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
D
D
Ihlenburg-Schwarz
Mosaiques-Diagnostics, Hannover, Germany.
J
J
Raad
Mosaiques-Diagnostics, Hannover, Germany.
A
A
Durban
Mosaiques-Diagnostics, Hannover, Germany.
M
M
Schiemann
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
C
C
Könecke
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
H
H
Diedrich
Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
E
E
Holler
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
G
G
Beutel
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.|Department of Hematology and Oncology, Klinikum Braunschweig, Braunschweig, Germany.
J
J
Krauter
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
A
A
Ganser
Department of Hematology, Hemostasis, Oncology and Stem cell transplantation, Hannover Medical School, Hannover, Germany.
M
M
Stadler
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010455:Peptides / Q000378:metabolism; D020543:Proteome; D040901:Proteomics / Q000379:methods; D012372:ROC Curve; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D014184:Transplantation, Homologous; D055815:Young Adult
D010455:Peptides; D020543:Proteome