The humoral response to vascular and nonvascular allografts of bone

The cytotoxic donor specific antibody response after vascularized and nonvascularized bone allograft implantation was assessed in rats and dogs. Nonvascularized segmental femoral grafts were studied in rats; nonvascularized fresh and cryopreserved massive osteochondral allografts were studied in dogs; and vascularized and nonvascularized fibular allografts were studied in dogs. The major histocompatibility complex antigens of all animals were defined. All grafts were stabilized by internal fixation and the antibody response was measured in a 51chromium release microcytotoxicity assay using donor lymphocytes as target cells. In all cases, donor specific antibody responses were elicited by major histocompatibility complex mismatched grafts. The response was directed primarily at Class I specificities although there was likely and antiClass II response as well. Among fully mismatched grafts, antidonor antibody was detectable earlier in animals receiving vascularized grafts (1 week after surgery) than in animals receiving nonvascularized grafts (3 weeks after surgery). Massive grafts elicited a sustained response whereas relatively smaller grafts, such as the fibula did not. The antidonor antigen antibody response was transient and less frequent in animals receiving frozen grafts. The clinical implications of these data are unclear. Although some improvement of clinical outcome has been observed with grafts matched for major histocompatibility complex antigens, the potential benefits of tissue antigen matching or modulation of the host immune response remain unresolved.