Differences between synthetic oligosaccharide immunoabsorbents in depletion capacity for xenoreactive anti-Gal alpha l-3Gal antibodies from human serum

Extracorporeal immunoabsorption for removal of anti-Gal alpha1-3Gal (anti-G al) antibodies in putative pig-to-human xenotransplantation is considered a major prophylactic measure to avoid hyperacute and acute vascular rejectio ns. However, the efficacy of the procedure does depend on choosing the appr opriate oligosaccharide epitopes for the binding of human anti-Gal. The syn thetic oligosaccharides Gal alpha1-3Gal (B-disaccharide, Bdi) and Gal alpha 1-Gal beta1-4Glc ('type 6' trisaccharide, Tri6), covalently coupled to Seph arose via polyacrylamide (Sorbents Bdi and Tri6, respectively), as well as a mixture thereof (Sorbent Mix), were examined for their efficacy to absorb anti-Gal from 20 human serum samples. Sorbent Bdi removed 81% of anti-Gal IgM and 85% of -IgG when assessed on Bdi by ELISA, but only 49% of IgG and 75% of IgM when assessed on Tri6. Sorbent Tri6 and -Mix showed significantl y better absorption capacities in so far as Sorbent Tri6 removed 65% of ant i-Gal IgM and 80% of -IgG as assessed on Bdi and 85% of IgM/87% of IgG when tested on Tri6, and Sorbent Mix absorbed > 90% anti-Gal of both isotypes o f either specificity. Direct hemagglutination of rabbit erythrocytes (E-R) was reduced by 75% (median value, range 0-94%) and the median cytotoxicity to PK15 target cells by > 94% after absorption on Sorbent Mix. Neither the decrease in E-R agglutination titers nor the reduction of PK15 cytotoxicity revealed significant differences between the three immunoabsorbents tested . The large variation ranges of absorption efficacies within the 20 tested sera suggest that "tailor-made" immunoabsorption treatments may be needed f or putative xenotransplant recipients.