Treatment With Riboflavin and Ultraviolet Light Prevents Alloimmunization to Platelet Transfusions and Cardiac Transplants

Abstract

Functional leukocytes in blood transfusions can cause alloimmunization. Previous studies have shown that exposure of platelet concentrates to riboflavin and light (Mirasol PRT treatment) causes irreparable modification of nucleic acids. This treatment does not interfere with platelet function but does inhibit a wide range of immunological functions of leukocytes present in platelet concentrates. The current study evaluated the ability of Mirasol treatment to prevent alloimmunization by platelet transfusions in rats. Lewis rats received eight transfusions of untreated or Mirasol-treated platelets containing leukocytes from DA rats. Animals were subsequently challenged with a heart transplant under cyclosporine treatment. Mirasol treatment caused apoptosis of the leukocytes as measured by annexin V and CD45 staining. Complement split products were deposited on the apoptotic bodies in the platelet pack. The primary and secondary immunoglobulin (Ig) M and IgG responses in rats that received Mirasol-treated platelets were almost completely abolished compared to animals that received untreated platelets. Untreated platelet transfusions elicited strong IgG responses that were associated with rapid rejection of subsequent heart transplants. Rejected hearts contained macrophage infiltrates and C4d deposits. In contrast, no grafts were rejected by recipients transfused with Mirasol-treated platelets. Macrophage infiltrates and C4d deposits were decreased in these grafts. Recipients that were presensitized to untreated platelets were capable of producing a memory response to Mirasol-treated platelets that caused accelerated rejection of subsequent transplants. Transfusions of platelets that were treated with riboflavin and ultraviolet light prevented presensitization to transplants. However, Mirasol-treated platelets were immunogenic in presensitized recipients.