RELATIONSHIP OF OKT3 SENSITIZATION AND VASCULAR REJECTION IN CARDIAC TRANSPLANT PATIENTS RECEIVING OKT3 REJECTION PROPHYLAXIS

Abstract

We prospectively and serially monitored plasma levels of OKT3 in 20 patients who were receiving 14- or 21-day rejection prophylaxis with OKT3. We retrospectively compared plasma OKT3 levels with biopsy scores assessed by light microscopy and immunofluorescence, clinical findings, human antimouse antibody (HAMA) production assessed by a blocking assay and by ELISA, and circulating immune complex levels assessed by a flow cytometric Raji cell assay. Using these methods, we evaluated the relationship of OKT3 sensitization, a humorally mediated immune response, to the development of vascular rejection in these patients. We found that 6 of 20 patients had declines in plasma OKT3 levels to less than 50% of their steady-state value before the conclusion of therapy (OKT3 consumption). This fall in plasma OKT3 preceded a significant rise in the CD 3 lymphocyte level by up to 3 days. All 6 patients showed HAMA production by either blocking or ELISA assay (P = less than 0.02) and developed vascular rather than cellular rejection (P = less than 0.01). OKT3 sensitization was significantly more common in patients treated with 21-day rejection prophylaxis (4 of 6 patients, P = less than 0.01). Only 4 of 14 other patients showed vascular rejection; 2 of these 4 also developed HAMA without OKT3 consumption and both had been treated with 21-day rejection prophylaxis with OKT3. None of the 20 patients showed significant levels of circulating immune complexes. This study demonstrates that OKT3 sensitization is strongly associated with vascular rejection. Vascular rejection was usually demonstrated 7 days after OKT3 consumption was seen and was coincident with HAMA production. By contrast, 4 patients without OKT3 sensitization had vascular rejection demonstrable in the early posttransplant period; in such patients, prospective immunofluorescence of biopsies was the only reliable indicator of this rejection type. The higher incidence of vascular rejection in these 20 patients was definitely related to the use of 21-day OKT3 rejection prophylaxis. Overall, 7 of the 12 patients treated with this regimen developed vascular rejection. Allograft and patient survival among patients with vascular rejection was significantly worse than in patients with cellular rejection (P = less than 0.01). Prospective monitoring of patients treated with OKT3 by serial plasma levels and by biopsy immunofluorescence will identify patients at risk for these types of humoral rejection.