What component of blood transfusion is most likely responsible for immunosuppression?

White Blood Cells are Responsible for Transfusion-Associated Immunosuppression

White blood cells (leukocytes) are the primary component of blood transfusions responsible for immunosuppression. 1

Mechanism of Transfusion-Associated Immunomodulation (TRIM)

• Transfusion-associated immunomodulation (TRIM) describes the pro-inflammatory or immunosuppressant effects of transfusions caused by donor's transfused components interacting with recipient cells 1
• Non-leukodepleted blood components contain cells presenting donor antigens coated in HLA-DR proteins that interact with recipient leukocytes, resulting in immune suppression or alloimmunization 1
• Following transfusion, leukocytes from the donor and the recipient interact, leading to immune suppression 1
• The immunosuppressive effect is likely due to anergy from presentation of large amounts of antigen through the intravenous route, favoring presentation by "nonprofessional" antigen-presenting cells 2

Evidence Supporting Leukocytes as the Primary Immunosuppressive Component

• Studies have demonstrated that the immunosuppressive effect requires the presence of viable leukocytes, as no suppression occurs when autologous blood is used in volunteers 3
• Research shows that transfusions using washed red blood cells significantly reduce pro-inflammatory cytokines (TNF, IL-6, IL-8, IL-12, IFN-γ, and IL-17A) in recipients 1
• Leukoreduction of cellular blood products has significantly reduced the incidence of immunological platelet transfusion refractoriness in leukemia patients 4
• Clinical evidence shows that allogeneic transfusions containing leukocytes are associated with increased risk for mortality and organ dysfunction in recipients 5

Clinical Implications of Transfusion-Induced Immunosuppression

• TRIM has been linked to increased rates of cancer recurrence (up to 80% in colorectal cancer) and postoperative bacterial infections (200-1000% increase in some studies) 2
• Immunosuppression following transfusion may be beneficial in certain contexts, such as improved outcomes in renal allograft transplantation 5
• The immunosuppressive effects appear to be dose-dependent, with a second transfusion leading to more pronounced and prolonged immunosuppression 3
• Leukoreduction practices have been implemented in many countries to reduce these immunomodulatory effects 4

Other Components and Their Effects

• Red blood cells alone do not appear to be the primary cause of immunosuppression, though storage lesions in RBCs may contribute to some immune effects 1
• Platelets may contribute to allergic reactions but are not the primary cause of immunosuppression 1
• Immunoglobulins in plasma components can cause reactions but are not the main driver of the immunosuppressive effect 1
• Soluble molecules like HLA class I and II and Fas ligand molecules released during storage may contribute to immunomodulating effects and induction of apoptosis 6

Prevention of Immunosuppressive Effects

• Leukodepletion (removal of white blood cells) from blood products has become standard practice in many countries to reduce immunomodulatory effects 4
• Irradiation of blood products with gamma radiation (minimum dose of 25 Gy) prevents transfusion-associated graft-versus-host disease by inactivating viable lymphocytes 1
• UV irradiation pathogen inactivation techniques can also damage DNA in contaminating lymphocytes, potentially eliminating the need for irradiation of platelet products 1