All ETDs from UAB

Advisory Committee Chair

A Joseph Tector Iii

Advisory Committee Members

Herbert Chen

David K C Cooper

James George

Robin Lorenz

Document Type

Dissertation

Date of Award

2019

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

In the United States, hundreds of thousands of patients suffer from end-stage organ failure or terminal diseases without the option of a life-saving transplant because of severe organ shortages. Xenotransplantation offers a possible solution by using genetically engineered pigs as organ donors. Application of pig-to-human organ transplantation has been limited by antibody-mediated rejection (AMR), but recent genetic engineering advances have eliminated pig glycan xenoantigens and dramatically reduced antibody binding. In human-to-human transplantation, allotransplantation, AMR is prevented by pretransplant screening donors and recipients. The major histocompatibility complex (MHC), class I and II, are primary targets for antibodies and may also bind the porcine MHC. This dissertation tested the antibody binding of waitlisted renal patients to three glycan knockout pigs and developed multiple models to study the impact of MHC class I antibodies in pig-to-human xenotransplantation. The findings identified patients with clinically acceptable and unacceptable levels of antibody binding, identified cross-species class I MHC antibodies, and identified methods to screen and eliminate class I MHC antigens. This work provides insights for initial histocompatibility testing and genetic engineering strategies.

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