Proceedings of the XVIITH World Congress of the Transplantation SocietySignificance of anti-gal IgG in chronic xenograft rejection
Section snippets
Anti-gal IgG production in chronic xenograft rejection
The long-term immune response in humans to α-gal epitope on pig xenografts could be studied in diabetic patients that were transplanted with cultured fetal pig pancreatic islet cell clusters.8 These patients were simultaneously transplanted with a kidney allograft and subjected to extensive immunosuppressive regimens. Analysis of anti-Gal activity in these patients demonstrated an average 50-fold increase in this antibody titer.9 Furthermore, the affinity of anti-Gal in these patients increased
Association between α-Gal epitope expression on xenograft and inflammatory infiltrates
Cartilage xenografts explanted from monkeys 2 months after transplantation contained extensive mononuclear inflammatory infiltrates that were comprised of approximately 70% T lymphocytes and 30% macrophages. Complete removal of α-gal epitopes from pig cartilage was achieved by incubation with 100 U/mL of recombinant α-galactosidase, for 4 hours at 26°C, followed by extensive washes to remove the enzyme.12 The recombinant enzyme was cloned from coffee beans and expressed in yeast.13 Monkeys
Endothelial cell activation by anti-gal
Palmetshofer et al14 incubated pig endothelial cells with sera from cynomolgus monkeys transplanted with pig cartilage, described earlier. Such incubation resulted in activation of the endothelial cells as indicated by the increased E-selection expression. Specific removal of anti-Gal from the sera eliminated their activating effect. Furthermore, sera obtained from the same monkeys prior to transplantation did not activate pig endothelial cells. These data imply that high-affinity anti-Gal
Conclusions
High-affinity anti-Gal IgG molecules produced in large amounts in response to α-gal epitopes in xenografts are detrimental to the xenograft and mediate chronic xenograft rejection. This antibody induces xenograft destruction by ADCC, by activation of the endothelial cells within the graft and by increasing activation of T cells against xenograft antigens.
Immunosuppressive drugs that effectively suppress allograft rejection fail to prevent production of the elicited high-affinity anti-Gal.
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Galactosyl-knock-out engineered pig as a xenogenic donor source of adipose MSCs for bone regeneration
2013, BiomaterialsCitation Excerpt :Lipoaspiration products were kept for a maximum of 90 min (mean 43 ± 21 min) at 4 °C until tissue digestion and the AMSC isolation procedure. Two different pig strains were used as AMSCs donors: Belgian Landrace pigs (as galactosyl-positive [Gal+] cells; Centre A. de Marbaix, Université catholique de Louvain, Louvain-la-Neuve, Belgium) and homozygous Gal-KO pigs (Xenome consortium research group, C. Galli/Italy; H. Niemman/Germany) [21]. Animals were housed separately in accordance with the guidelines of the Belgian Ministry of Agriculture and Animal Care.
Distribution of the Alpha-Gal Epitope on Adult Porcine Bone Tissue
2006, Transplantation ProceedingsCitation Excerpt :In the chronic xenograft rejection of meniscus cartilage, high-affinity anti-Gal IgG molecules are produced in large amounts in response to alpha-Gal epitopes in xenografts. This antibody induces xenograft destruction by ADCC, by activation of endothelial cells within the graft, and by increased activation of T cells against xenograft antigens.6 Just like cartilage xenografts, we presumed that alpha-Gal epitopes may also induce acute vascular rejection and chronic rejection in bone xenografts.
Identification of peptide mimetics of xenoreactive α-Gal antigenic epitope by phage display
2006, Biochemical and Biophysical Research CommunicationsTolerance induction by lentiviral gene therapy with a nonmyeloablative regimen
2006, BloodCitation Excerpt :All mammals except humans, apes, and old-world monkeys express α1,3 galactosyltransferase (GalT), hence Galα1,3Galβ1, 4GlcNac-R (αGal) is expressed on most tissues including vascular endothelium.2-4 However, as humans have natural antibodies (Abs) against αGal, it is known that xenotransplantation of pig organs into humans induces hyperacute rejection, acute vascular rejection/delayed xenograft rejection, and even chronic rejection against αGal.5-7 In pig-to-primate discordant combination, 80% to 90% of antipig xenogeneic Abs are anti-αGal Abs.8
Carbohydrates in transplantation
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