Factors Influencing RBC Alloimmunization: Lessons Learned from Murine Models

Abstract

Red blood cell (RBC) alloimmunization may occur following transfusion or pregnancy/delivery. Although observational human studies have described the immunogenicity of RBC antigens and the clinical significance of RBC alloantibodies, studies of factors influencing RBC alloimmunization in humans are inherently limited by the large number of independent variables involved. This manuscript reviews data generated in murine models that utilize transgenic donor mice, which express RBC-specific model or authentic human blood group antigens. Transfusion of RBCs from such donors into nontransgenic but otherwise genetically identical recipient mice allows for the investigation of individual donor or recipient-specific variables that may impact RBC alloimmunization. Potential donor-related variables include methods of blood product collection, processing and storage, donor-specific characteristics, RBC antigen-specific factors, and others. Potential recipient-related variables include genetic factors (MHC/HLA type and polymorphisms of immunoregulatory genes), immune activation status, phenotype of regulatory immune cell subsets, immune cell functional characteristics, prior antigen exposures, and others. Although murine models are not perfect surrogates for human biology, these models generate phenomenological and mechanistic hypotheses of RBC alloimmunization and lay the groundwork for follow-up human studies. Long-term goals include improving transfusion safety and minimizing the morbidity/mortality associated with RBC alloimmunization.

Characteristics of Extracellular Vesicles in Red Blood Concentrates Change with Storage Time and Blood Manufacturing Method

“…It has been suggested that the characteristics of EVs can vary among the blood products due to the variation in the blood processing methods [51,52]. An article by Bakkour et al [19] highlighted some feasible reasons to explain the variation in EV characteristics between RCF and WBF RCCs, including variability in the temperature and the lengths of pre-processing storage time as well as leukoreduction technique.…”

Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn

“…10 Once exposed, the maternal immune system may or may not respond to foreign red cell antigens. 11 The immune response to red cell antigens is complex and not fully understood. It is clear that the RhD antigen is the most potent immunogen of all of the red cell antigens; 85% of RhD-negative individuals will sensitize (form anti-D) after challenge with a 200 mL transfusion of red cells, although more recent data suggests this is far lower.…”

Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems

“…In transfusion medicine, immune responses to allogeneic RBCs represent a significant obstacle to multiple transfusions in clinical practice. Despite decades of experience in the transfusion of RBCs and the observation of a multitude of allo-antibodies thereafter, the precise mechanisms by which transfused RBCs induce alloantibody formation in certain individuals and in certain clinical scenarios remain to be fully understood and they are the subject of extensive investigation and are reviewed elsewhere [34,35]. …”