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.
RBC alloimmunization, or the formation of antibodies to ?non-self? RBC antigens, may occur through transfusion or pregnancy and may be dangerous in both settings. The 4 synergistic PPG projects will investigate unique questions surrounding RBC alloimmunization, with Core B providing leukoreduced, quality tested, transgenic murine RBCs expressing model or authentic human blood group antigens for transfusion; Core B will also serve as a central immunohematology reference laboratory. The long term goals of this PPG, relevant to public health, include a better understanding of the induction and consequences of RBC alloimmunization, such that targeted strategies for mitigation can be developed.
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| Maier, Cheryl L; Mener, Amanda; Patel, Seema R et al. (2018) Antibody-mediated immune suppression by antigen modulation is antigen-specific. Blood Adv 2:2986-3000 |
| Mener, Amanda; Patel, Seema R; Arthur, Connie M et al. (2018) Complement serves as a switch between CD4+ T cell-independent and -dependent RBC antibody responses. JCI Insight 3: |
| Mener, Amanda; Arthur, Connie M; Patel, Seema R et al. (2018) Complement Component 3 Negatively Regulates Antibody Response by Modulation of Red Blood Cell Antigen. Front Immunol 9:676 |
