POSTTRANSPLANT ANTIBODIES AND FRESH VENOUS ALLOGRAFT FAILURE IN DOGS

Small diameter arterial reconstruction is usually achieved by use of t he autologous long saphenous vein. As an alternative to this blood con duit, the venous allograft has been used with some success in the past , but is likely to be the target of an immune rejection reaction from the host. This study was designed to characterize humoral-immune react ions possibly involved in the outcome of venous allografts. Ten mongre l dogs received a histoincompatible femoral vein allograft and an auto graft as interposition grafts to both femoral arteries. They were inve stigated for donor-specific antibody development using donor splenocyt es and cultured vascular endothelial cells (EC). Serum samples were co llected at surgery, at 2 weeks, and every month until graft occlusion occurred. All autografts were patent at retrieval except one, and all allografts underwent thrombosis. In all dogs, donor-specific IgG devel opment was observed that appeared specifically at 4 weeks and lasted u ntil graft occlusion was detected. All reactive sera were cytotoxic to donor EC except one, and this reactivity was completely lost after se rum absorption on donor splenocytes. This latter absorption resulted i n the total loss of flow cytometric reactivity against donor EC in 3 d ogs, whereas a low reactivity was still present in 4 dogs. Immunoblott ing analysis showed a posttransplant reactivity against various protei n bands on donor EC. Absorption of the reactive serum on donor splenoc ytes resulted in the loss of reactivity to proteins of similar to 40, 30, and 22 kDa in most experiments. Moreover, as demonstrated by immun ofluorescence on cryostat sections of explanted grafts, IgG deposition was seen mainly in the media and the adventitia of the allografts but not in autografts. These results suggest that a donor-specific antibo dy response directed mainly against MHC antigens might play a role in the thrombosis of histoincompatible venous allografts, thus decreasing the patency rate.