title: Accurate diagnosis of acute graft-versus-host disease using serum proteomic pattern analysis.
abstract: 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.
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
authors.forename: Ramaprasad
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Jasmine
authors.initials: J
authors.lastname: Daniels
authors.forename: Vincent
authors.initials: V
authors.lastname: Fusaro
authors.forename: Andreas
authors.initials: A
authors.lastname: Lundqvist
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Killian
authors.forename: David
authors.initials: D
authors.lastname: Geho
authors.forename: Martha
authors.initials: M
authors.lastname: Quezado
authors.forename: David
authors.initials: D
authors.lastname: Kleiner
authors.forename: Sally
authors.initials: S
authors.lastname: Rucker
authors.forename: Virginia
authors.initials: V
authors.lastname: Espina
authors.forename: Gordon
authors.initials: G
authors.lastname: Whiteley
authors.forename: Lance
authors.initials: L
authors.lastname: Liotta
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Petricoin
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.forename: Ben
authors.initials: B
authors.lastname: Hitt
authors.forename: A J
authors.initials: AJ
authors.lastname: Barrett
authors.forename: Kevin
authors.initials: K
authors.lastname: Rosenblatt
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
mesh_terms: 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
chemical_list: D015415:Biomarkers; D001798:Blood Proteins