CD25 Saturation Rate in Heart Transplant Patients Receiving Two-Dose Daclizumab Induction

Abstract

CD25 (the α-subunit of the IL-2-receptor, IL-2Rα) is only expressed on activated T cells and is crucial to the clonal expansion of anti-allograft host lymphocytes that mediate acute rejection. Specific anti-CD25 monoclonal antibodies, such as daclizumab (Zenapax, Hoffman LaRoche, Mississauga, Ontario, Canada) bind to but do not stimulate IL-2Rα, thereby inhibiting the host immune response against the allograft (1). A two-dose daclizumab-induction regimen has been shown to be effective in preventing acute rejection in solid organ transplantation (1–4). To our knowledge, CD25 saturation has not been studied in heart transplant recipients receiving daclizumab-induction. We report the results of a prospective pilot study of the CD25 saturation rate of peripheral blood lymphocytes in heart transplant patients receiving two-dose daclizumab-induction. Written informed consent was obtained for three women and two men (range 43–66 years). Patients received daclizumab-induction consisting of 2 mg/kg at the time of transplant and 1 mg/kg on postoperative day 14. Maintenance immunosuppression therapy consisted of corticosteroids, mycophenolate mofetil (Cell-Cept Hoffman LaRoche), and a calcineurin inhibitor (cyclosporine in three patients and tacrolimus in two). CD25 expression was measured by flow cytometry (Beckman-Colter XL/MCL) with saturation defined as a percent expression of CD25 ≤2%. Acute rejection was defined as grade ≥3A, according to the International Society of Heart and Lung Transplantation classification (5). Primary endpoints were the CD25 percent expression and the incidence of acute rejection. The mean CD25 percent expression (±SD) pretransplant was 23%±14% and subsequently 1%±2%, 2%±3%, 7%±9%, 1%±1%, 3%±4%, and 3%±2% on postoperative days 14, 28, 42, 56, 70, and 84, respectively. The CD25 saturation rate of peripheral blood CD4 lymphocytes in each of the five patients is shown in Figure 1.FIGURE 1. CD25 percent-expression in five heart transplant patients receiving daclizumab-induction.One patient (20%) experienced an acute rejection episode (grade 3A) on day 84 posttransplant that reversed on high-dose methylprednisolone. This patient (Patient 4) had a 0% CD25 expression by flow cytometry on all measures except on the last measurement at 84 days when the CD25 percent expression was 4%. Both patients 2 and 3 had unpredictable CD25 saturation rates throughout follow-up; patient 2 having had multiple CD25 percent expression measurements >2% but without experiencing an acute rejection episode during the 3-month follow-up period. Two-dose daclizumab-induction in kidney transplant recipients has been found to result in effective CD25 saturation for up to 70 days (1). However, in our heart transplant patients receiving the same daclizumab-induction regimen, CD25 saturation occurred unpredictably. Nevertheless, several studies have shown support for two-dose daclizumab-induction for the prophylaxis of acute graft rejection in solid organ transplantation (1–3), including in heart transplant patients in our own experience (4). To our knowledge, the direct correlation of the CD25 saturation rate to the incidence of acute rejection has not been reported. Despite the attractive theoretical basis for the assumption of a link, prospective studies are needed to determine what level of CD25 blockade is required for adequate acute rejection prophylaxis. In addition, the value of CD25 percent expression measurements in solid organ transplant patients receiving two-dose daclizumab-induction and its usefulness as a predictor of acute graft rejection remain to be evaluated prospectively. Brian J. Potter Nadia Giannetti Jean-Pierre Routy Renzo Cecere Marcelo Cantarovich Departments of Medicine and Cardiovascular and Thoracic Surgery, Multi-Organ Transplant Program, Royal Victoria Hospital, McGill University Health Center, McGill University, Montréal, Québec, Canada