Solving the dilemma of prevention of red cell alloimmunization.

Evaluation of: Stephen J, Cairns LS, Pickford WJ, Vickers MA, Urbaniak SJ, Barker RN. Identification, immunomodulatory activity and immunogenicity of the major helper T cell epitope on the K blood group antigen. Blood 119(23), 5563-5574 (2012). Alloimmunization to blood group antigens is a major concern in transfusion medicine. This occurs when antigen-mismatched blood is transfused into a recipient lacking a red blood cell antigen that is expressed on the donor red blood cells. Alloimmunization in this case can result in future problems in finding compatible blood for transfusion and can cause hemolytic transfusion reactions. Alloimmunization can also occur in instances where a mother lacks a red blood cell antigen that is carried by the fetus. In these cases, alloimmunization can result in an antibody that can cross the placenta and cause moderate-to-severe problems in the fetus or newborn due to hemolytic anemia and/or inhibition of hematopoiesis. This is called hemolytic disease of the fetus and newborn. Stephen et al. describe a unique approach to producing a peptide tolerogen to prevent alloimmunization to a specific blood group antigen, K, in the Kell blood group system. They identify an immunodominant K peptide and use this peptide to show that it strongly stimulates human T helper cells from K-immunized people in vitro and that it shows efficacy when used as a nasal tolerogen to suppress immunization with K protein in a mouse model. These results open the door for therapies aimed at the prevention and/or treatment of alloimmunization in both a transfusion setting and, importantly, in hemolytic disease of the fetus and newborn.