Antibodies against hyaluronan oligosaccharides in xenotransplantation

Abstract

Carbohydrate‐specific antibodies are significant mediators of xenograft rejection. This study analyzed the carbohydrate specificity of antibodies in baboons before and after xenotransplantation of organs or injection of porcine red blood cells from hDAF transgenic pigs, using a glycan array with structurally defined glycans. Antibodies against hyaluronic acid disaccharide (HA2) showed the highest reactivity at baseline and rose after xenogeneic exposure. We also investigated in the serum of baboons that underwent xenotransplantation with either hDAF or hDAF/hMCP transgenic pig organs and Lewis rats after hamster‐skin xenotransplantation the specificity of anti‐HA antibodies on a glycan microarray representing HA oligosaccharides containing from two to 40 saccharides. Notably, the HA oligosaccharides ranging from 32 to 40 saccharides exhibited the highest antibody binding intensities at baseline in baboon and rat sera. After xenotransplantation, antibodies against HA38 and HA40 in baboons, and HA32, HA34, and HA36 in rats showed the highest titer increases. The changes of anti‐HA IgM and IgG antibodies in rats after skin xenotransplantation was also confirmed by an ELISA specific for HA2, HA24, and HA85 antibodies. Thus, xenotransplantation is associated with increased antibodies against HA‐oligosaccharides, which may represent a new target for intervention.

Serum antibody screening using glycan arrays

“…Using a 406-component CFG glycan microarray, Bello-Gil et al screened serum from baboons before and after receiving a red blood cell injection, heart xenotransplantation, or kidney xenotransplantation from transgenic pigs. 325 The authors identified numerous antibodies—each with a different glycan target—present at high levels before transplantation. Notably, many of these antibodies further increased in reactivity after transplant, with antibodies targeting the hyaluronan disaccharide showing the greatest increase relative to pre-transplant levels.…”

Developments in kidney xenotransplantation

“…Natural and inducible anti-SDa plays important roles in GTKO pig-to-rhesus monkey xenotransplant rejection, thus providing further support for the notion that Gal and SDa antigens should be simultaneously targeted ( 35 ). Exploration of new key non-α-Gal antigens is currently underway ( 36 ).…”