Transfusion-Induced Bone Marrow Transplant Rejection Due to Minor Histocompatibility Antigens

Abstract

Traditionally, alloimmunization to transfused blood products has focused exclusively upon recipient antibodies recognizing donor alloantigens present on the cell surface. Accordingly, the immunological sequelae of alloimmunization have been antibody mediated effects (i.e. hemolytic transfusion reactions, platelet refractoriness, anti-HLA and anti-HNA effects, etc.). However, in addition to the above sequelae, there is also a correlation between the number of antecedent transfusions in humans and the rate of bone marrow transplant (BMT) rejection - under reduced intensity conditioning with HLA matched or HLA identical marrow. BMT of this nature is the only existing cure for a series of non-malignant hematological diseases (e.g. sickle cell disease, thalassemias, etc.); however, rejection remains a clinical problem. It has been hypothesized that transfusion induces subsequent BMT rejection through immunization. Studies in animal models have observed the same effect and have demonstrated that transfusion induced BMT rejection can occur in response to alloimmunization. However, unlike traditional antibody responses, sensitization in this case results in cellular immune effects, involving populations such as T cell or NK cells. In this case, rejection occurs in the absence of alloantibodies, and would not be detected by existing immune-hematological methods. We review human and animal studies in light of the hypothesis that, for distinct clinical populations, enhanced rejection of BMT may be an unappreciated adverse consequence of transfusion which current blood bank methodologies are unable to detect.

Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases

“…Animal models indicate that in the setting of MHC-matched transplantation, rejection induced by transfusion-related alloimmunization is mediated primarily by T cells [39]. Given the challenges to demonstrating donor-directed cellular immunity clinically, we did not attempt to assess it.…”

Mechanisms of red blood cell transfusion‐related immunomodulation

“…MHC II molecules function to present processed antigens and activate lymphocytes. After transfusion, interactions between donor MHC II molecules on residual WBCs and recipient lymphocytes may result in either alloimmunization or immune suppression . Features such as the degree of HLA compatibility, the functionality of donor APCs, and the inflammatory state of the recipient likely determine whether residual allogeneic WBCs induce immune tolerance or alloimmunization .…”

Establishing the hematopoietic stem cell transplant (HSCT) in a developing country; the journey of HSCT in Semarang, Indonesia

“…Patients being treated according to our BMT protocol are treated with filtered and irradiated blood products. Irradiated products are cytomegalovirus-safe, have a reduced risk of nonhemolytic febrile transfusion and alloimmunization, and have a reduced incidence of transfusion-associated graft vs host disease in at-risk individuals [18][19][20][21].…”