Research Project
9360038
Project Summary Background: RBC alloimmunization is a clinically significant problem in transfusion and pregnancy settings alike. Given the number of variables involved in human studies, the projects in this PPG have taken the approach of using reductionist murine models to generate a better overall understanding of factors influencing RBC alloimmunization. This proposed Mouse Blood Center Core (Core B) will support the 4 PPG projects by providing leukoreduced, quality controlled, transgenic RBCs for transfusion. Further, this Core will serve as a central immunohematology reference Laboratory for alloantibody testing. In addition to optimizing resource utilization and efficiency, the products and services provided by this Core will allow for more direct comparison of results between sites and projects. Innovation: The mouse donor strains proposed for use in these studies, generated and characterized by PPG investigators, allow for isolation of the effects of single variable changes on alloimmunization. The HOD donors have a triple fusion protein on their RBCs, composed of hen egg lysozyme, ovalbumin, and the human Duffyb antigen. The KEL donors have the entire human KEL glycoprotein expressed in an RBC specific manner, with K1 as well as K2 donors being used in this proposal. Antibodies generated by wild type recipient mice transfused with transgenic HOD, K1, or K2 RBCs are clinically significant, resulting in premature RBC clearance, hemolytic transfusion reactions, and hemolytic disease of the fetus and newborn (HDFN). Specific Aim 1: To breed and maintain transgenic mice expressing model or human blood group antigens on their RBCs. Specific Aim 2: To collect, process, perform quality control measures, and distribute donor RBCs from these transgenic animals to all 4 PPG sites. Specific Aim 3: To serve as an immunohematology reference laboratory for antibody detection.
