Prediction of successful allograft rejection retreatment with OKT3

Abstract

OKT3 is considered to be effective in the prophylaxis and treatment of rejection. However, anti-OKT3 immunization is still a major side-effect. Only the IgG antiidiotypic component of the response is responsible for neutralization of OKT3 therapeutic activity by inhibiting OKT3's binding to T cells (i.e., blocking antibodies). It has recently been reported that successful OKT3 retreatment could be performed in patients showing circulating anti-OKT3 antibodies assessed by ELISA, which does not distinguish between blocking and nonblocking antibodies. The aim of this study was to investigate the role of these two types of anti-OKT3 antibodies for their capacity to interfere with effective OKT3 retreatment. Twelve cadaver renal allograft recipients who received OKT3 inducing therapy, were given a second 10 day-course of OKT3 for treatment of rejection. Circulating CD3+ cells were sequentially monitored. Anti-OKT3 antibodies were detected by using both conventional ELISA and an immunofluorescence inhibition test specifically detecting blocking antibodies. OKT3 and the patient's serum were incubated for 30 min at 4 degrees C, and 2 x 10(5) normal T cells were added (30 min at 4 degrees C). After washing, the cells were incubated with FITC goat antimouse antiserum. Fluorescent cells were counted using a FACS analyzer. In 10 patients, at the end of the 10-day second course, less than 10% circulating CD3+ cells were detected. None of these patients had detectable antibodies in the IF inhibition assay at the beginning of retreatment, irrespective of anti-OKT3 antibody titers detected by ELISA. In contrast, in two patients, OKT3 therapy was ineffective: more than 50% circulating CD3+ cells were detected and OKT3 treatment had to be interrupted soon after it was initiated. In both of them, blocking antibodies were detected by the IF-inhibition assay. These results suggest that specific detection of blocking antiidiotypic antibodies by the IF inhibition assay is a reliable parameter for predicting the feasibility of OKT3 retreatment, avoiding misuse of this expensive therapy.