title: Evaluation of the tolerability and immunogenicity of ultraviolet C-irradiated autologous platelets in a dog model.
abstract: BACKGROUND
  The THERAFLEX ultraviolet (UV) platelets (PLTs) pathogen reduction system for PLT concentrates (PCs) operates using ultraviolet C (UVC) light at a wavelength of 254 nm. UVC treatment can potentially alter proteins, which may affect drug tolerance in humans and influence the immunogenicity of blood products. This preclinical study in beagle dogs was designed to evaluate the safety pharmacology of UVC-irradiated PCs after intravenous administration and to determine whether they are capable of eliciting humoral responses to PLTs and plasma proteins.
  
  
  METHODS
  Six beagle dogs each were transfused once every other week for 10 weeks with UVC-irradiated or nonirradiated PCs. All PCs were autologous canine single-donor products prepared from whole blood. Safety pharmacology variables were regularly assessed. The impact of UVC irradiation on PLT and plasma proteomes was analyzed by one- and two-dimensional gel electrophoresis. Serum samples were tested for UVC-induced antibodies by Western blot and flow cytometry.
  
  
  RESULTS
  Dogs transfused with UVC-irradiated PCs showed no signs of local or systemic intolerance. Few but significant changes in PLT protein integrity were observed after UVC irradiation. Even after repeated administration of UVC-irradiated PCs, no antibodies against UVC-exposed plasma or PLT proteins were detected.
  
  
  CONCLUSIONS
  Repeated transfusions of autologous UVC-treated PCs were well tolerated in all dogs studied. UVC irradiation did not cause significant plasma or PLT protein modifications capable of inducing specific antibody responses in the dogs. High-resolution proteomics combined with antibody analysis introduces a comprehensive and sensitive method for screening of protein modifications and antibodies specific for pathogen reduction treatment.
authors.affiliation: German Red Cross Blood Service NSTOB, Institute Springe, Springe, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Pohler
authors.forename: Jörg
authors.initials: J
authors.lastname: Lehmann
authors.forename: Verena
authors.initials: V
authors.lastname: Veneruso
authors.forename: Janina
authors.initials: J
authors.lastname: Tomm
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Bernd
authors.initials: B
authors.lastname: Lambrecht
authors.forename: Barbara
authors.initials: B
authors.lastname: Kohn
authors.forename: Christiane
authors.initials: C
authors.lastname: Weingart
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Müller
authors.forename: Axel
authors.initials: A
authors.lastname: Seltsam
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001792:Blood Platelets / Q000276:immunology* / Q000528:radiation effects*; D001798:Blood Proteins / Q000276:immunology; D058731:Blood Safety / Q000379:methods; D001804:Blood Transfusion, Autologous; D004285:Dogs; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology; D008297:Male; D023421:Models, Animal; D017713:Platelet Transfusion / Q000379:methods*; D040901:Proteomics; D014466:Ultraviolet Rays
chemical_list: D000906:Antibodies; D001798:Blood Proteins