Antigen expression in xenotransplantation: how low must it go?

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Parker, W; Lin, SS; Platt, JL

Published Date

  • January 27, 2001

Published In

Volume / Issue

  • 71 / 2

Start / End Page

  • 313 - 319

PubMed ID

  • 11213079

International Standard Serial Number (ISSN)

  • 0041-1337

Language

  • eng

Conference Location

  • United States