Destructive and protective effects of antibody on transplants in humans: practical and theoretical considerations.

Clearly the pioneering studies on hyperacute rejection, which lead to the concept of antibody-mediated injury to transplants, still present challenges to the clinician today. It is obvious that tests for antibodies before and after transplantation must be further refined to more reliably distinguish among destructive, protective and innocuous antibodies. The current crossmatch tests detect antibodies to donor lymphocytes, but lymphocytes may not always represent adequately the antigenic composition of the tissue that will be transplanted. Moreover the distribution of antigens in transplanted tissues must be considered in relation to the functional anatomy of the organs in order to understand the ultimate effects of antibodies on specific transplants. Thus some antibodies that produce a positive crossmatch may be safely ignored because they exert either a beneficial or no effect on the organ that is to be transplanted, while other antibodies that remain undetected by crossmatches on lymphocytes may damage some types of transplants. Moreover, the balance between protective and destructive antibodies is not dynamic; with time potentially dangerous antibody responses may be inhibited by a variety of autoregulatory mechanisms, some of which may be mediated by antibodies. Regulatory as well as cytotoxic antibody production may be actively stimulated by pretransplant blood transfusions. These antibody-mediated immune responses probably are magnified in the clinical setting by our current therapeutic immunosuppressive drugs which have more impact on cell-mediated immunity than on antibody-mediated mechanisms. New immunosuppressive interventions devised to inhibit undesired antibody-mediated immune responses might be of benefit to those patients who fail to respond to current rejection therapy as well as to patients who have pre-existing antibodies and are waiting for transplants.