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


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.
Division of Transplantation Surgery and William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA.
Brian K
BK
Goh
Marcio F
MF
Chedid
James M
JM
Gloor
Suresh
S
Raghavaiah
Mark D
MD
Stegall
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D000077552:Basiliximab; D003167:Complement Activation / Q000187:drug effects; D051056:Complement Inactivating Agents / Q000008:administration & dosage*; D004347:Drug Interactions / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy* / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D051056:Complement Inactivating Agents; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; C481642:eculizumab