W Parker1, S S Lin, J L Platt. 1. Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Abstract
BACKGROUND: Acute vascular rejection (AVR) is an important immunological barrier to xenotransplantation. Thought to be initiated by xenoreactive antibodies, acute vascular rejection might, in principle, be avoided by engineering animals to express low levels of antigen. The extent to which antigen expression would have to be decreased to achieve such a goal is unknown. METHODS: We estimated the decrease in expression of a xenogeneic antigen, Galalpha1-3Gal, which might be needed to avert acute vascular rejection of xenotransplants based on the decrease in antibody binding to endothelium that would prevent tissue damage. RESULTS: The level of decrease needed in Galalpha1-3Gal expression needed to avoid acute vascular rejection was estimated to exceed 96% of baseline. The extent of the decrease needed reflected, in part, a substantial "excess" of Galalpha1-3Gal on porcine endothelial cell surfaces. CONCLUSIONS: Although the change in antigen expression required to avoid acute vascular rejection might be conditioned by various factors, the very large magnitude of this change necessitates application of highly efficient approaches to antigen modification.
BACKGROUND: Acute vascular rejection (AVR) is an important immunological barrier to xenotransplantation. Thought to be initiated by xenoreactive antibodies, acute vascular rejection might, in principle, be avoided by engineering animals to express low levels of antigen. The extent to which antigen expression would have to be decreased to achieve such a goal is unknown. METHODS: We estimated the decrease in expression of a xenogeneic antigen, Galalpha1-3Gal, which might be needed to avert acute vascular rejection of xenotransplants based on the decrease in antibody binding to endothelium that would prevent tissue damage. RESULTS: The level of decrease needed in Galalpha1-3Gal expression needed to avoid acute vascular rejection was estimated to exceed 96% of baseline. The extent of the decrease needed reflected, in part, a substantial "excess" of Galalpha1-3Gal on porcine endothelial cell surfaces. CONCLUSIONS: Although the change in antigen expression required to avoid acute vascular rejection might be conditioned by various factors, the very large magnitude of this change necessitates application of highly efficient approaches to antigen modification.
Authors: Jon Kobashigawa; Maria G Crespo-Leiro; Stephan M Ensminger; Hermann Reichenspurner; Annalisa Angelini; Gerald Berry; Margaret Burke; Lawrence Czer; Nicola Hiemann; Abdallah G Kfoury; Donna Mancini; Paul Mohacsi; Jignesh Patel; Naveen Pereira; Jeffrey L Platt; Elaine F Reed; Nancy Reinsmoen; E Rene Rodriguez; Marlene L Rose; Stuart D Russell; Randy Starling; Nicole Suciu-Foca; Jose Tallaj; David O Taylor; Adrian Van Bakel; Lori West; Adriana Zeevi; Andreas Zuckermann Journal: J Heart Lung Transplant Date: 2011-03 Impact factor: 10.247