Accurate diagnosis of acute graft-versus-host disease using serum proteomic pattern analysis.
OBJECTIVE
The rapid diagnosis of acute graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) is important for optimizing the management of this life-threatening complication. Current diagnostic techniques are time-consuming and require invasive tissue sampling. We investigated serum protein pattern analysis using surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectrometry as a tool to diagnose GVHD.


METHODS
Eighty-eight serum samples were obtained from 34 patients undergoing HCT either pretransplant (n = 28 samples) or at various time points posttransplant (n = 60 samples), including 22 samples obtained on the day of onset of acute GVHD symptoms. Serum proteomic spectra generated from a "training set" of known samples were used to identify distinct proteomic patterns that best categorized a sample as either pretransplant, posttransplant non-GVHD, or GVHD; these distinct proteomic signatures were subsequently used to classify samples from a masked "test" sample set into the appropriate diagnostic category.


RESULTS
Proteomic pattern analysis accurately distinguished GVHD samples from both posttransplant non-GVHD samples and pretransplant samples (100% specificity and 100% sensitivity in both cases). Furthermore, distinct serum proteomic signatures were identified that distinguished pretransplant from posttransplant non-GVHD samples (100% specificity and 94% sensitivity).


CONCLUSIONS
These preliminary data suggest a potential application of SELDI-TOF-based proteomic analysis as a rapid and accurate method to diagnose acute GVHD.
Srinivasan
Ramaprasad
R
Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
Daniels
Jasmine
J
Fusaro
Vincent
V
Lundqvist
Andreas
A
Killian
Jonathan K
JK
Geho
David
D
Quezado
Martha
M
Kleiner
David
D
Rucker
Sally
S
Espina
Virginia
V
Whiteley
Gordon
G
Liotta
Lance
L
Petricoin
Emmanuel
E
Pittaluga
Stefania
S
Hitt
Ben
B
Barrett
A J
AJ
Rosenblatt
Kevin
K
Childs
Richard W
RW
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000628:therapy; D011237:Predictive Value of Tests; D040901:Proteomics; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014184:Transplantation, Homologous
D015415:Biomarkers; D001798:Blood Proteins