Use of Donor Serum to Prevent Passive Transfer of Hyperacute Rejection

Abstract

Organ transplantation in presensitized recipients continues to be contraindicated for heart and kidney recipients due to the risk of hyperacute rejection, which has no known treatment at this time. We tested whether donor serum, which contains solubie MHC class I antigen, is able to neutralize the effect of antidonor antibody in the recipient and prevent hyperacute or accelerated rejection. A rat model of passive immunization was used to test the role of anti-donor antibody in hyperacute rejection. Seven of 10 recipients of hyperimmune serum (HyS), derived from Lewis rats (ETI 1 ) following 3 ACI (RT1") skin grafts, developed hyperacute or accelerated rejection. intravenous injec* tion of ACI serum prior to the HyS administration prevented hyperacute rejection in all recipients tested. When third-party (Wistar-Furth, RTl tt ) serum was given to Lewis rats injected with HyS, hyperacute rejection was not abrogated. When examining the mechanism of this effect, a simple antibody blocking phenomenon was found to be unlikely since flow cytometry analysis showed that ACI serum needed to be present at >256-fold excess compared to HyS to block anti-ACI antibody binding to RTl.A'-f-cells by 50%. We tested whether the RT1.A* class I antigen in ACI serum had other biologic properties that resulted in the prolonged graft survivah However, removal of RT1.A* antigen from ACI serum prior to use in the passive transfer model did not abrogate the graft Prolongation observed previously. These data suggest that components of donor serum other than MHC class I antigen may be useful for preventing the antibody-mediated component of hy per acute rejection. ® 199-1 Acndemie Frew, Inc.

Therapeutic Effect of Y-27632 on Chronic Allograft Nephropathy in Rats

“…Lewis rats (LEW, RT1 1 ) (200 to 250 g) acted as kidney graft recipients and Fisher rats (F344, RT1 1v1 ) (200 to 250 g) as donors. The surgical procedure was performed as previously described [15]. Briefly, rats were anesthetized by 0.3% barbital sodium 30 mg/kg body weight intraperitoneally.…”