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Eur J Cardiothorac Surg 1998;14:197-200
© 1998 Elsevier Science NL

Vascular rejection post heart transplantation is associated with positive flow cytometric cross-matching¹

^a Department of Thoracic and Cardiovascular Surgery, Section of Cardiac Transplantation and Mechanical Circulatory Assist Program, Cleveland Clinic Foundation, Cleveland, Ohio, USA
^b Histocompatibility Laboratory Transplant Center, Cleveland Clinic Foundation, Cleveland, Ohio, USA
^c The Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
^d Department of Cardiology, Section of Heart Failure, Cleveland Clinic Foundation, Cleveland, Ohio, USA

Received 6 October 1997; received in revised form 14 April 1998; accepted 12 May 1998.

Corresponding author. Transplant Center Histocompatibility Laboratory, Desk L12, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. Tel.: +1 216 444 2805; fax: +1 216 444 8261; e-mail djc@tt.ccf.org

Objective: Use of flow cytometry cross-matching for measurement of donor-specific alloreactivity and monitoring anti-donor antibodies is well established. This study was performed to determine (1) its accuracy as a marker of vascular rejection, (2) its correlation with post-transplant outcome and (3) its ability to monitor highly sensitized patients requiring antibody removal with plasma exchange. Methods: Serial serum samples from 99 heart transplant recipients were examined for the presence of anti-donor antibodies of the IgG class that were reactive with T and/or B cryopreserved donor lymphocytes. A sub-group of 20 HLA sensitized patients required plasma exchange to remove the anti-HLA antibodies and were monitored with flow cytometry cross-matching to assess the degree of antibody removal. Results: Positive T-cell reactions were observed in 26 patients and positive B-cell reactions in 54. Twenty patients had vascular rejection. A significantly larger number of patients with a positive flow cytometry cross-match had vascular rejection (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 sensitivity of 55%), and 17 had a positive B-cell reaction (sensitivity of 85%). Of the 79 patients who did not develop vascular rejection, 64 had a negative T-cell reaction (specificity of 81%), and 42 had a negative B-cell reaction (specificity of 53%). The actuarial 2-year survival estimates were significantly higher in patients with negative T-cell reactions (90% versus 75%; P=0.04), and B-cell reactions (95% versus 78%; P=0.02). In the highly sensitized subgroup (n=20) the effectiveness 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 detection of vascular rejection after cardiac transplantation. Quantitative measurements may allow evaluation of the efficacy of treatment modalities employed in the management of vascular rejection in an attempt to improve outcome.

Key Words: Flow cytometry cross-match • Vascular rejection • Cardiac transplant

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