title: Generation of inflammatory cytokines and chemokines from peripheral blood mononuclear cells by HLA Class II antibody-containing plasma unit that was associated with severe nonhemolytic transfusion reactions.
abstract: BACKGROUND
  HLA Class II antibodies are thought to be involved in severe transfusion reactions including transfusion-related acute lung injury (TRALI). The activation of monocytes by HLA Class II antibody may play an important role in the etiology of TRALI.
  
  
  METHODS
  An 81-year-old man with non-Hodgkin's lymphoma (Clinical Stage IIIA) received a plateletpheresis unit containing at least 4 x 10(11) platelets because of thrombocytopenia and a bleeding tendency. Approximately 30 minutes after the start of transfusion, he developed chills, tachycardia, dyspnea, lumber, and abdominal pain and then a fever (40.3 degrees C). His SaO(2) dropped to 70 percent. The transfusion was discontinued immediately. His symptoms disappeared after treatment with oxygen and the administration of corticosteroid and aminophyrine. A chest X-ray showed no sign of pulmonary edema.
  
  
  RESULTS
  The donor serum sample had HLA-DR antibodies against multiple DR antigens including DR13, the recipient's HLA-DR type. The cross-match between the patient's lymphocytes and the donor serum was positive. The treatment of peripheral blood mononuclear cells from healthy subjects bearing DR13 antigen with the donor plasma caused the secretion of inflammatory cytokines (i.e., interleukin [IL]-1beta, IL-6, and tumor necrosis factor-alpha) and neutrophil-activating chemokines (i.e., IL-8 and CXCL1/GRO-alpha) in a cognate antigen-antibody relationship. In addition, the secretion of inflammatory cytokines appeared to require the involvement of CD32 and/or CD16.
  
  
  CONCLUSIONS
  HLA-DR antibodies, detected in this case, had biologic functions to induce production of not only inflammatory cytokines but also neutrophil-attractant chemokines in vitro, which could contribute to the etiology of severe nonhemolytic transfusion reactions.
authors.affiliation: Japanese Red Cross, Hokkaido Red Cross Blood Center, and Aiiku Hospital, Sapporo, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Sakagawa
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Fujihara
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sato
authors.forename: Miki
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Kanji
authors.initials: K
authors.lastname: Fukai
authors.forename: Masanobu
authors.initials: M
authors.lastname: Morioka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Azuma
authors.forename: Hisami
authors.initials: H
authors.lastname: Ikeda
mesh_terms: D000208:Acute Disease; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000097:blood*; D001792:Blood Platelets / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008171:Lung Diseases / Q000209:etiology*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000276:immunology; D017713:Platelet Transfusion / Q000009:adverse effects*
chemical_list: D000906:Antibodies; D000941:Antigens; D018925:Chemokines; D016207:Cytokines; D006684:HLA-DR Antigens; D018836:Inflammation Mediators