Immunological Features in the Process of Blood Platelet-Induced Alloimmunisation, with a Focus on Platelet Component Transfusion

Abstract

Alloimmunisation to platelet antigens is not uncommon; a large number of females, having had pregnancies, developed antibodies to Human Leukocyte Antigen (HLA) moieties harboured on their foetuses’ cells (inherited from the father(s)) that may conflict with further pregnancies and transfused Platelet Components occasionally. This is possible since platelets constitutionally express HLA class I molecules (though in copy numbers that consistently differ among individuals). Platelets also express HPA moieties that are variants of naturally expressed adhesion and aggregation molecules; HPA differences between mothers and foetuses and between donors and recipients explain alloimmune conflicts and consequences. Lastly, platelets express ABO blood group antigens, which are rarely immunising, however transfusion mismatches in ABO groups seem to be related to immunisation in other blood and tissue groups. Transfusion also brings residual leukocytes that may also immunise through their copious copy numbers of HLA class I (rarely class II on activated T lymphocytes, B cells, and dendritic cells). In addition, residual red blood cells in platelet concentrates may induce anti-red blood cell allo-antibodies. This short review aims to present the main mechanisms that are commonly reported in alloimmunisation. It also critically endeavours to examine paths to either dampen alloimmunisation occurrences or to prevent them.

Pathogen-reduced PRP blocks T-cell activation, induces Treg cells, and promotes TGF-β expression by cDCs and monocytes in mice

“…22 Both platelets and contaminating leukocytes contribute to the alloantibody responses in platelet transfusion. 23,24 Alloantibody responses result from complex interactions of innate and adaptive cellular responses that involve antigen-presenting cells (APCs) such as macrophages (Mfs), conventional dendritic cells (cDCs), and B cells, and their cognate T cells. 23,25,26 While advances have been made in understanding the cellular immune response to red blood cell (RBC) transfusions, less is known about the mechanisms regulating cellular responses against allogeneic platelets.…”

“…23,24 Alloantibody responses result from complex interactions of innate and adaptive cellular responses that involve antigen-presenting cells (APCs) such as macrophages (Mfs), conventional dendritic cells (cDCs), and B cells, and their cognate T cells. 23,25,26 While advances have been made in understanding the cellular immune response to red blood cell (RBC) transfusions, less is known about the mechanisms regulating cellular responses against allogeneic platelets. [27][28][29][30] Platelets can incite inflammatory responses due to factors such as platelet storage lesion, platelet-specific surface receptors, and platelet-expressed products, [31][32][33][34][35][36] leading to adverse transfusion reactions, including allergic reactions, febrile nonhemolytic reactions, sepsis, and transfusion-associated acute lung injury.…”

Dominant immune response to HLA‐B57/B58 molecules after platelet transfusion

“…1 Platelet refractoriness is a serious complication that can have both nonimmune and immune causes, including the production of alloantibodies against class I HLA molecules. 2 Anti-class I HLA may react with the transfused platelets, impeding their function and decreasing their survival. The incidence of HLA alloimmunization may reach 60% in patients requiring repeated platelet transfusions, decreasing transfusion performance and leading to the development of platelet transfusion refractoriness.…”

“…2 In France, leukoreduction is mandatory for transfusion, so the most important cellular source of HLA molecules in platelet concentrates (PCs) is the platelets themselves. 2 Differences in HLA molecule expression on the platelet surface, with potential consequences for immunogenicity, have recently been reported. 4 CD4 + T cells are involved in red blood cell (RBC) alloimmunization and have also been shown to play a major role in anti-HLA alloimmunization in a mouse model.…”

Seroconversion of red blood cell antibody in ABO-incompatible living donor liver transplantation -a case report-

“…In this case, the patient developed the RBC antibody after platelet transfusion without pregnancy or RBC transfusion. Platelets express a few RBC antigens that rarely generate antibodies, and there can be residuals or fragments of RBCs remaining in the platelet concentrates [5,9].…”