Use of agal Oligosaccharides in Xenotransplantation

The relevance of glycoproteins extends into the fundamentals of many important biological processes including fertilization, immune defense, viral replication, parasitic infection, cell growth, cell-cell adhesion, degradation of blood clots, and inflammation [28-31]. Anti-Gal immunoadsorption and neutralization are two practical uses of a-gal oligosaccharides in xenotransplantation. For immunoadsorption, a potential recipient is depleted of anti-Gal by passing the blood through an affinity column containing a-gal epitopes [32,33]. A number of pig-to-primate organ xeno-transplantations following anti-Gal immunoadsorption were reported. This procedure was shown to extend the survival of pig organs from 1 to 23 days. Recently it was discovered that antibody heterogeneity made the depletion of all anti-Gal in human serum difficult [7]. McKane and coworkers found that immunoadsorbents derived from pentasaccharide 4 or trisaccharide 3 were effective for IgG removal in all individuals. For IgM, no single immunoadsorbent achieved complete removal. For example, pentasaccharide 4 immunoadsorbent removes anti-Gal IgM in only 30% of individuals. Interestingly, 3-deoxy-trisaccharide a-d-Galp-(1^3)-^-d-Galp-(1^4)-^-d-[3deoxy]GlcNAcp and 6-deoxy-trisaccharide a-d-Galp-(1^3)-^-d-Galp-(1^4)-^-d-[6deoxy]GlcNAcp were the best single immunoadsorbents for IgM removal. The two deoxy derivatives were completely successful in 73% of individuals. The polymorphic nature of the anti-Gal repertoire poses a considerable challenge when one is trying to develop an efficient antibody removal system. So far the best

Figure 1 Xenotransplantation hindered by a-gal epitopes (1-4 ) and the anti-Gal antibody.

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