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Eliminating Xenoantigen Expression on Swine RBC
Zheng-Yu Wang1, Gregory R Martens, Ross L Blankenship
11 Department of Surgery, Indiana University School of Medicine, Indianapolis, IN. 2 Department of Surgery, Indiana University Health, Indianapolis, IN. 3 Indiana University Health Transplant Institute, Indianapolis, IN.
Transplantation
|July 6, 2016
Summary
Genetic engineering can reduce human antibody binding to pig cells, potentially overcoming xenotransplantation barriers. Gene knockouts in swine red blood cells (RBC) show reduced xenoreactivity, approaching autologous levels.
Area of Science:
- Immunology
- Transplantation Biology
- Genetic Engineering
Background:
- Xenotransplantation faces a humoral immune barrier due to human antibody binding to donor tissues.
- Genetic engineering tools offer potential solutions to overcome this barrier.
- Hypothesis: Reducing human antibody binding to xenogeneic (swine) cells to levels seen in allogeneic (human) transplantation is achievable.
Purpose of the Study:
- To analyze human antibody binding to swine red blood cells (RBC) from genetically engineered (knockout) pigs.
- To compare this binding to human antibody binding on allogeneic and autologous human RBC.
- To assess the feasibility of gene inactivation in reducing xenogeneic antigenicity.
Main Methods:
- Incubation of human sera with swine and human RBC.
- Quantification of human IgG and IgM antibody binding using flow cytometry and mass spectrometry.
- Comparison of antibody binding levels between genetically modified swine RBC and human RBC.
Main Results:
- Mass spectrometry showed 3 gene inactivations reduced human antibody binding to swine RBC to levels comparable to autologous human RBC.
- Flow cytometry indicated RBC from 2-gene knockout swine had lower human antibody binding than some allogeneic human RBC.
- Further gene deletion in pigs resulted in significantly reduced xenoreactivity compared to alloreactivity in 30% of samples.
Conclusions:
- Gene disruption effectively eliminates xenoantigenicity of swine RBC.
- The gene knockout approach shows promise for reducing antigenicity in other pig tissues.
- This strategy may enable overcoming the humoral immune barrier for successful xenotransplantation.
