title: Novel human radiation exposure biomarker panel applicable for population triage.
abstract: OBJECTIVE
  To identify a panel of radiation-responsive plasma proteins that could be used in a point-of-care biologic dosimeter to detect clinically significant levels of ionizing radiation exposure.
  
  
  METHODS
  Patients undergoing preparation for hematopoietic cell transplantation using radiation therapy (RT) with either total lymphoid irradiation or fractionated total body irradiation were eligible. Plasma was examined from patients with potentially confounding conditions and from normal individuals. Each plasma sample was analyzed for a panel of 17 proteins before RT was begun and at several time points after RT exposure. Paired and unpaired t tests between the dose and control groups were performed. Conditional inference trees were constructed based on panels of proteins to compare the non-RT group with the RT group.
  
  
  RESULTS
  A total of 151 patients (62 RT, 41 infection, 48 trauma) were enrolled on the study, and the plasma from an additional 24 healthy control individuals was analyzed. In comparison with to control individuals, tenascin-C was upregulated and clusterin was downregulated in patients receiving RT. Salivary amylase was strongly radiation responsive, with upregulation in total body irradiation patients and slight downregulation in total lymphoid irradiation patients compared with control individuals. A panel consisting of these 3 proteins accurately distinguished between irradiated patients and healthy control individuals within 3 days after exposure: 97% accuracy, 0.5% false negative rate, 2% false positive rate. The accuracy was diminished when patients with trauma, infection, or both were included (accuracy, 74%-84%; false positive rate, 14%-33%, false negative rate: 8%-40%).
  
  
  CONCLUSIONS
  A panel of 3 proteins accurately distinguishes unirradiated healthy donors from those exposed to RT (0.8-9.6 Gy) within 3 days of exposure. These findings have significant implications in terms of triaging individuals in the case of nuclear or other radiologic events.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Bazan
authors.affiliation: SRI International, Menlo Park, California.
authors.forename: Polly
authors.initials: P
authors.lastname: Chang
authors.affiliation: SRI International, Menlo Park, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Balog
authors.affiliation: SRI International, Menlo Park, California.
authors.forename: Annalisa
authors.initials: A
authors.lastname: D'Andrea
authors.affiliation: SRI International, Menlo Park, California.
authors.forename: Thomas
authors.initials: T
authors.lastname: Shaler
authors.affiliation: SRI International, Menlo Park, California.
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.affiliation: SRI International, Menlo Park, California.
authors.forename: Shirley
authors.initials: S
authors.lastname: Lee
authors.affiliation: SRI International, Menlo Park, California.
authors.forename: Travis
authors.initials: T
authors.lastname: Harrison
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Lei
authors.initials: L
authors.lastname: Shura
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Lucy
authors.initials: L
authors.lastname: Schoen
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
authors.affiliation: SRI International, Menlo Park, California. Electronic address: david.cooper@sri.com.
authors.forename: David E
authors.initials: DE
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000681:Amylases / Q000032:analysis / Q000528:radiation effects*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D051152:Clusterin / Q000097:blood / Q000528:radiation effects*; D015536:Down-Regulation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007239:Infections / Q000097:blood; D007938:Leukemia / Q000097:blood / Q000628:therapy; D015182:Lymphatic Irradiation; D008223:Lymphoma / Q000097:blood / Q000628:therapy; D008297:Male; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000628:therapy; D019095:Point-of-Care Systems; D011829:Radiation Dosage; D012463:Saliva / Q000201:enzymology; D019063:Tenascin / Q000097:blood / Q000528:radiation effects*; D019172:Transplantation Conditioning; D014218:Triage; D015854:Up-Regulation; D014916:Whole-Body Irradiation; D014947:Wounds and Injuries / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D051152:Clusterin; D019063:Tenascin; D000681:Amylases