The impact of terminal complement blockade on the efficacy of induction with polyclonal rabbit antithymocyte globulin in living donor renal allografts

BackgroundEculizumab, a potent inhibitor of terminal complement activation, appears promising in reducing early antibody-mediated rejection in positive crossmatch kidney transplantation. However, its concomitant use with polyclonal rabbit antithymocyte globulin (rATG) might reduce the efficacy of rATG. This study aimed to evaluate the effect of eculizumab on the efficacy of rATG in vivo and determine the role of complement in rATG-induced lymphocyte cell depletion.Patients and methodsThirty-six kidney transplant recipients were classified into 3 groups according to induction regime: anti-IL-2 receptor antibody alone induction group (basiliximab, n = 8); rATG induction (n = 20), and rATG + eculizumab induction group (n = 8). Peripheral blood T-cell subsets and NK cells were measured 3–4 days after transplant (after 3 doses of rATG).ResultsCompared to anti-IL-2 receptor antibody induction group, both groups treated with rATG demonstrated significant depletion of all T-cell subsets (CD3-positive cells) (P < 0.0001 for rATG vs. anti-IL-2 receptor antibody induction group; P < 0.001 for rATG + eculizumab vs. anti-IL-2 receptor antibody group). However, while T-cell counts were low in all rATG-treated patients, eculizumab treatment resulted in higher peripheral blood T-cell counts in rATG treated patients (P = 0.005). Before induction, median total lymphocyte counts were normal for the three study groups. By 1, 4 months and 1 year, median the total lymphocyte count was normal for the anti-IL-2 receptor antibody group but was below normal range or at the lower edge of normality for rATG and rATG + eculizumab groups.ConclusionsThis small-sample size study suggests that peripheral T cells are depleted by rATG in the presence of terminal complement inhibition. However, eculizumab appears to have a mild inhibitory effect on peripheral blood T-cell depletion by rATG in kidney transplant recipients.

► Eculizumab was used concomitantly with rabbit antithymocyte globulin rATG.
► Peripheral T-cells are depleted by rATG in the presence of complement inhibition.
► Eculizumab had a mild inhibitory effect on peripheral T-cell depletion by rATG.