VASCULAR REJECTION POST HEART-TRANSPLANTATION IS ASSOCIATED WITH POSITIVE FLOW CYTOMETRIC CROSS-MATCHING

Objective: Use of flow cytometry cross-matching for measurement of don or-specific alloreactivity and monitoring anti-donor antibodies is wel l established. This study was performed to determine (1) its accuracy as a marker of vascular rejection, (2) its correlation with posttransp lant outcome and (3) its ability to monitor highly sensitized patients requiring antibody removal with plasma exchange. Methods: Serial seru m samples from 99 heart transplant recipients were examined for the pr esence of anti-donor antibodies of the IgG class that were reactive wi th T and/or B cryopreserved donor lymphocytes. A sub-group of 20 HLA s ensitized patients required plasma exchange to remove the anti-HLA ant ibodies and were monitored with flow cytometry cross-matching to asses s the degree of antibody removal. Results: Positive T-cell reactions w ere observed in 26 patients and positive B-cell reactions in 54. Twent y patients had vascular rejection. A significantly larger number of pa tients with a positive flow cytometry cross-match had vascular rejecti on (42% versus 12% for T-cell reactions, and 32% versus 7% for B-cell reactions; P = 0.002 each). Of the patients who had vascular rejection , 11 had a positive T-cell reaction (flow cytometry cross-match sensit ivity of 55%), and 17 had a positive B-cell reaction (sensitivity of 8 5%). Of the 79 patients who did not develop vascular rejection, 64 had a negative T-cell reaction (specificity of 81%), and 42 had a negativ e B-cell reaction (specificity of 53%). The actuarial 2-year survival estimates were significantly higher in patients with negative T-cell r eactions (90% versus 75%; P = 0.04), and B-cell reactions (95% versus 78%; P = 0.02). In the highly sensitized subgroup (n = 20) the effecti veness of plasma exchange to decrease anti-HLA antibody reactivity was a strong predictor of outcome. For patients in whom plasma exchange ( PE) reduced anti-donor reactivity, 1-year survival was 87% compared to 25% in those whom PE did not reduce the level of antibody binding as assessed with flow cytometry cross-matching (P < 0.0001). Conclusions: Flow cytometry cross-matching provides a valuable marker for the dete ction of vascular rejection after cardiac transplantation. Quantitativ e measurements may allow evaluation of the efficacy of treatment modal ities employed in the management of vascular rejection in an attempt t o improve outcome. (C) 1998 Elsevier Science B.V. All rights reserved.