Proteomic patterns predict acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
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.
Weissinger
Eva M
EM
Hannover Medical School, Department of Hematology, Hemostasis, and Oncology, Hannover, Germany. mischak-weissinger.eva@mh-hannover.de
Schiffer
Eric
E
Hertenstein
Bernd
B
Ferrara
James L
JL
Holler
Ernst
E
Stadler
Michael
M
Kolb
Hans-Jochem
HJ
Zander
Axel
A
Zürbig
Petra
P
Kellmann
Markus
M
Ganser
Arnold
A
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
D010455:Peptides