Inhibition of xenoreactive natural antibody production by retroviral gene therapy.
basic_science · Level V
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Abstract
The major barrier to transplantation across discordant species, such as from pig to human, is rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate epitope Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5'-diphosphate galactose:beta-D-galactosyl-1, 4-N-acetyl-D-glucosaminide alpha(1-3)galactosyltransferase (E.C. 2.4.1.151), or simply alphaGT. When a functional alphaGT gene was introduced by retroviral gene transfer into bone marrow cells, alphaGal XNA production in a murine model ceased. Thus, genetic engineering of bone marrow may overcome humoral rejection of discordant xenografts and may be useful for inducing B cell tolerance.
Medical subject headings
- Antibody Formation
- Bone Marrow Cells
- Epitopes
- Galactosyltransferases
- Genetic Therapy
- Graft Rejection
- Transplantation, Heterologous