title: Immunomodulatory effects of blood transfusions: the synergic role of soluble HLA Class I free heavy-chain molecules detectable in blood components.
abstract: BACKGROUND
  Over the past decades, the weight of the published literature demonstrates that blood transfusions can induce clinically significant immunosuppression in recipients. Several studies showed significant improved clinical outcomes in the patients receiving leukoreduced transfusions, compared with control patients who received nonleukoreduced transfusions. Moreover, the immunosuppressive potential of blood products grows with the time of their storage and becomes highest in nonleukoreduced blood products stored for a long time.
  
  
  METHODS
  The interest was previously focused on the determination of immunomodulatory soluble molecules such as soluble HLA Class I (sHLA-I) and soluble Fas ligand (sFasL) in different blood components and on the evaluation of their immunomodulatory activities. On this basis, whether soluble beta2-microglobulin free HLA Class I heavy chains (sHLA-beta2fHC) could be detected and immunochemically characterized in different blood components was evaluated. Immunomodulatory activity of detectable sHLA-beta2fHC molecules was evaluated by apoptosis inducing capacity in interleukin-2-activated antigen-specific cytotoxic T lymphocytes (CTL).
  
  
  RESULTS
  Double-determinant immunoenzymatic assay indicates that sHLA-beta2fHC levels in red blood cells stored for up to 30 days and in random-donor platelets are significantly (p < 0.001) higher than in other blood components, and the immunochemical characterization suggests that the major source of sHLA-beta2fHC molecules might be the residual white cells that undergo membrane damage during storage. Finally, allogeneic CD8+ CTL apoptosis induction confirmed biofunctionality of sHLA-beta2fHC molecules.
  
  
  CONCLUSIONS
  These data are comparable with those previously reported dealing with contaminant soluble molecules in allogeneic and autologous blood components, suggesting that sHLA-beta2fHC molecules could contribute to the immunosuppressive effects of blood transfusions.
authors.affiliation: Department of Internal Medicine, University and San Martino Hospital of Genoa, Genoa, Italy. mghio@unige.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Ghio
authors.forename: Paola
authors.initials: P
authors.lastname: Contini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ubezio
authors.forename: Clemente
authors.initials: C
authors.lastname: Mazzei
authors.forename: Franco
authors.initials: F
authors.lastname: Puppo
authors.forename: Franco
authors.initials: F
authors.lastname: Indiveri
mesh_terms: D017209:Apoptosis / Q000276:immunology; D001793:Blood Preservation; D001804:Blood Transfusion, Autologous / Q000009:adverse effects; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology; D053222:Fas Ligand Protein / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000097:blood* / Q000276:immunology; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000276:immunology; D007519:Isoantigens / Q000097:blood / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000821:virology; D065227:Transfusion Reaction; D001613:beta 2-Microglobulin / Q000097:blood / Q000276:immunology; D019014:fas Receptor / Q000097:blood / Q000276:immunology
chemical_list: D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D007155:Immunologic Factors; D007376:Interleukin-2; D007519:Isoantigens; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D019014:fas Receptor