Differences between synthetic oligosaccharide immunoabsorbents in depletion capacity for xenoreactive anti-Galalpha1-3Gal antibodies from human serum.

Extracorporeal immunoabsorption for removal of anti-Galalpha1-3Gal (anti-Gal) antibodies in putative pig-to-human xenotransplantation is considered a major prophylactic measure to avoid hyperacute and acute vascular rejections. However, the efficacy of the procedure does depend on choosing the appropriate oligosaccharide epitopes for the binding of human anti-Gal. The synthetic oligosaccharides Galalpha1-3Gal (B-disaccharide, Bdi) and Galalpha1-3Galbeta1-4Glc ('type 6' trisaccharide, Tri6), covalently coupled to Sepharose 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 significantly better absorption capacities in so far as Sorbent Tri6 removed 65% of anti-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 of either specificity. Direct hemagglutination of rabbit erythrocytes (ER) 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 ER 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 for putative xenotransplant recipients.