Human and non-human primate anti-galactosyl response after injection of rat monoclonal antibody bearing galactosyl epitopes

In the case of clinical use of pig-to-human xenografting, any exogenous sou rce of a-galactosyl epitopes will elicit an anti-galactosyl immune response , which could be deleterious for the xenograft. The presence of Gal alpha(1 -3)Gal residues was thus examined by western blotting on various rat monocl onal antibodies (mAb), which are used in clinical trials. In parallel, the anti-galactosyl humoral response was assessed in the serum of kidney allogr aft recipients and experimental baboons, which received these mAbs. Galacto syl residues were evidenced on all rat monoclonal antibody tested. The anti -galactosyl response was weak in kidney allograft recipients receiving a ba sic immunosuppression (Cyclosporine, Azathioprine, Prednisolone) and iterat ive injections of rat mAbs. In contrast, untreated or immunosuppressed babo ons that received rat mAbs developed a major anti-galactosyl humoral respon se. These results suggest that anti-galactosyl sensitization produced by th erapeutic agents will have to be considered in the case of clinical xenotra nsplantation.