Abstract
Reliable predictors of impending renal allograft rejection would be valuable for better patient management. To date, no available test has been shown to be consistently predictive and results have often been conflicting. We evaluated an effector of cell-mediated immunity, antibody-dependent cell-mediated cytotoxicity (ADCC) as well as the response of these cells to different biological response modifiers (BRM) in patients following renal allograft transplantation. The in vitro test used assayed monocytes as ADCC effector cells against antibody-sensitized chicken red blood cells. The effects of BRM were studied by preincubating the monocytes with lymphoblastoid IFN, recombinant α2-interferon or γ-interferon. A follow-up study was performed on 47 patients with end-stage renal disease treated with renal allograft transplantation. ADCC activity and its response to BRM were assayed prior to transplantation, 2, 4, and 9 weeks post transplantation. In the case of rejection, ADCC was then studied prior to initiation of antirejection therapy and for 2 months following treatment of rejection episode. We noted that in patients with stable grafts, the ADCC activity as well as its response to BRM declined gradually during the first 2 weeks post grafting and remained decreased up to 3 months after transplantation. In contrast, in recipients who experienced rejection episodes there was a sustained and significant increase in ADCC response to BRM during the first 3 weeks post grafting. By the time the diagnosis of rejection had been established the baseline ADCC activity had also increased. Following treatment and stabilization of the graft, ADCC activity and its response to BRM was decreased, similar to that in patients with stable grafts. Thus, by monitoring ADCC and the effect of different BRM on this activity we could predict rejection episodes in renal allograft recipients as early as 15 days in advance of any clinical or biochemical sign of rejection.