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 source of to-galactosyl epitopes will elicit an anti-galactosyl immune response, which could be deleterious for the xenograft. The presence of Galalpha(1-3)Gal residues was thus examined by western blotting on various rat monoclonal antibodies (mAb), which are used in clinical trials. In parallel, the anti-galactosyl humoral response was assessed in the serum of kidney allograft recipients and experimental baboons, which received these mAbs. Galactosyl residues were evidenced on all rat monoclonal antibody tested. The anti-galactosyl response was weak in kidney allograft recipients receiving a basic immunosuppression (Cyclosporine, Azathioprine, Prednisolone) and iterative injections of rat mAbs. In contrast, untreated or immunosuppressed baboons that received rat mAbs developed a major anti-galactosyl humoral response. These results suggest that anti-galactosyl sensitization produced by therapeutic agents will have to be considered in the case of clinical xenotransplantation.