title: Allergic agonists in apheresis platelet products are associated with allergic transfusion reactions.
abstract: BACKGROUND
  The mechanisms that underlie allergic transfusion reactions (ATRs) are not well characterized, but likely involve recipient, donor, and product factors. To assess product factors associated with ATRs, we investigated candidate mediators in apheresis platelet (PLT) products associated with ATRs and controls.
  
  
  METHODS
  Using bead-based and standard enzyme-linked immunosorbent assays, we tested supernatants from 20 consecutive apheresis PLT transfusions associated with ATRs and 30 control products for concentrations of mediators in three categories: acute inflammatory mediators, direct agonists of basophils and mast cells, and growth and/or priming factors of basophils and mast cells.
  
  
  RESULTS
  Median concentrations of the direct allergic agonists C5a, brain-derived neurotrophic factor (BDNF), and CCL5 (RANTES) were 16.6, 41.8, and 13.9% higher, respectively, in the supernatant of apheresis PLT products that were most strongly associated with ATRs (p < 0.05 for each mediator). Other direct agonists (macrophage inflammatory protein-1α, monocyte chemotactic protein-1, eotaxin-1, interleukin-8) were similar between groups. Concentrations of acute inflammatory mediators and basophil growth and/or priming factors were also similar between groups (p > 0.2 for all associations).
  
  
  CONCLUSIONS
  The allergic agonists C5a, BDNF, and CCL5 may be mediators of ATRs in apheresis PLT products. Acute inflammatory proteins and basophil and/or mast cell growth and priming factors do not appear to be associated with apheresis PLT products that cause ATRs.
authors: Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. wsavage1@jhmi.edu
authors: William J
authors: WJ
authors: Savage
authors: Jessica H
authors: JH
authors: Savage
authors: Aaron A R
authors: AA
authors: Tobian
authors: Chris
authors: C
authors: Thoburn
authors: Robert G
authors: RG
authors: Hamilton
authors: John T
authors: JT
authors: Schroeder
authors: Paul M
authors: PM
authors: Ness
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000276:immunology; D054413:Chemokine CCL11 / Q000097:blood / Q000276:immunology; D018932:Chemokine CCL2 / Q000097:blood / Q000276:immunology; D054405:Chemokine CCL3 / Q000097:blood / Q000276:immunology; D018946:Chemokine CCL5 / Q000097:blood / Q000276:immunology; D015936:Complement C5a / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000209:etiology* / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D017713:Platelet Transfusion / Q000009:adverse effects*; D010983:Plateletpheresis / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C515456:CCL11 protein, human; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a; D007371:Interferon-gamma