Gal/non‐Gal antigens in pig tissues and human non‐Gal antibodies in the GalT‐KO era1

Breimer ME. Gal/non‐Gal antigens in pig tissues and human non‐Gal antibodies in the GalT‐KO era. Xenotransplantation 2011; 18: 215–228. © 2011 John Wiley & Sons A/S.Abstract:  Our knowledge regarding Gal and non‐Gal antigens in GalT‐KO pig tissues can be summarized as α3Galactosyl‐tranferase gene knock out eliminates the Galα3Galβ4GlcNAc‐R antigen expression in pig tissues as well as anti‐Gal antibody binding. Other Galα‐terminating saccharides (e.g. iGb3 glycolipids and Galα2 determinants) may be present but have not been documented. α3Galactosyl‐tranferase gene knock out slightly changes the carbohydrate antigen expression but no “new” antigens recognized by the human immune system have been found. Non‐Gal antigens are both of protein and carbohydrate nature but their exact chemical structures are poorly defined. Regarding human non‐Gal antibodies our knowledge is as Non‐Gal antibodies exist naturally and increase in humans/non‐human primate (NHP) receiving WT or GalT‐KO pig grafts. Non‐Gal antibodies with new antigen epitope recognition can be induced in humans/NHP after challenge by WT or GalT‐KO pig grafts. Non‐Gal antibodies react with both carbohydrates and proteins. Part of the protein reactivity is directed to glycoprotein carbohydrates chains. Non‐Gal antibodies reacting with neuraminic acid terminated saccharides (both N‐Acetyl and N‐Glycoloyl variants) are present in humans/NHP. Anti‐neuraminic acid antibodies are increased, as well as induced, after grafting pig organs into humans/NHP. Non‐Gal antibodies does not cause hyperacute xenorejection but can be cytotoxic and cause xenoorgan damage. If humans sensitized to HLA antigens are at a higher risk of rejecting pig xenograft compared with non‐sensitized individuals is not fully clarified.Clinical trials are needed to evaluate the relevance of non‐Gal antigens/antibodies and for the xenofield to advance.