Immunomodulatory effects of blood transfusions: The synergic role of soluble HLA Class I free heavy-chain molecules detectable in blood components

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. STUDY DESIGN AND 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 β₂-microglobulin free HLA Class I heavy chains (sHLA-β₂fHC) could be detected and immunochemically characterized in different blood components was evaluated. Immunomodulatory activity of detectable sHLA-β₂fHC 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-β₂fHC 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-β₂fHC molecules might be the residual white cells that undergo membrane damage during storage. Finally, allogeneic CD8+ CTL apoptosis induction confirmed biofunctionality of sHLA-β₂fHC molecules. CONCLUSION: These data are comparable with those previously reported dealing with contaminant soluble molecules in allogeneic and autologous blood components, suggesting that sHLA- β₂fHC molecules could contribute to the immunosuppressive effects of blood transfusions.