TY - JOUR
T1 - The impact of terminal complement blockade on the efficacy of induction with polyclonal rabbit antithymocyte globulin in living donor renal allografts
AU - Goh, Brian K.
AU - Chedid, Marcio F.
AU - Gloor, James M.
AU - Raghavaiah, Suresh
AU - Stegall, Mark D.
PY - 2012/10
Y1 - 2012/10
N2 - Background: Eculizumab, 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 methods: Thirty-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). Results: Compared 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. Conclusions: This 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.
AB - Background: Eculizumab, 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 methods: Thirty-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). Results: Compared 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. Conclusions: This 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.
KW - Eculizumab
KW - Kidney transplantation
KW - Positive crossmatch
KW - Rabbit antithymocyte globulin
KW - Thymoglobulin
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UR - http://www.scopus.com/inward/citedby.url?scp=84868362664&partnerID=8YFLogxK
U2 - 10.1016/j.trim.2012.07.002
DO - 10.1016/j.trim.2012.07.002
M3 - Article
C2 - 22813834
AN - SCOPUS:84868362664
SN - 0966-3274
VL - 27
SP - 95
EP - 100
JO - Transplant Immunology
JF - Transplant Immunology
IS - 2-3
ER -