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Intracellular RBC Antigens Can Enhance RBC Alloimmunization in Mice

June 14, 2023

RBC alloimmunization from transfusions or pregnancy can be life threatening.  Currently, scientists have identified 43 polymorphic RBC surface antigen systems, and some are more immunogenic than others. Furthermore, there is a poor understanding of why most patients do not develop alloantibodies and why others respond to one or several antigens.  To gain a better understanding of the pathogenesis of alloimmunization, Jajosky et al. developed a mouse model.  Previously, they have shown that one RBC surface antigen can prime the immune system to enhance alloimmunization of another unrelated surface antigen.  In a paper recently published in the journal Blood, Jajosky et al. show that priming to an unlinked cytosolic protein can enhance the alloimmunization to an unrelated RBC surface antigen.  Key experiments in mice demonstrated that B cells from transgenic mice internalize green florescent protein (GFP) from transfused RBCs.  Furthermore, they show that immune priming to intracellular GFP enhances alloimmunization to two different RBC surface antigens—human Duffy and glycophorin A.  While it is not currently feasible to screen for intracellular RBC antigens, these studies provide insights into the development of alloimmunization and may eventually provide clues to prevent organ rejection and autoimmunity as well as treating hemolytic disease of the fetus and newborn.

References:

  1. R Jajosky, SR Patel, SC Wu, K Patel, et al. Prior immunization against an intracellular antigen enhances subsequent red blood cell alloimmunization in mice. Blood 2023; 141 (21): 2642–2653.
  2. Richard J. Benjamin; Cytosolic antigens prime RBC alloantibodies. Blood2023; 141 (21): 2550–2551.   

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