title: Inhibition of xenoreactive natural antibody production by retroviral gene therapy.
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.
authors.affiliation: Cellular and Molecular Biology Program, Allegheny University of the Health Sciences, 2900 Queen Lane, Philadelphia, PA 19129, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Bracy
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: J
authors.initials: J
authors.lastname: Iacomini
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000201:enzymology*; D016026:Bone Marrow Transplantation; D002460:Cell Line; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology*; D005700:Galactosyltransferases / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D051379:Mice; D018345:Mice, Knockout; D012190:Retroviridae / Q000235:genetics; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D000939:Epitopes; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase