title: Prolonged lymphocyte depletion by single-dose rabbit anti-thymocyte globulin and alemtuzumab in kidney transplantation.
abstract: Although antibody induction has gained in popularity, two agents are rarely combined. We retrospectively analyzed peripheral lymphocyte phenotypes of renal transplant recipients who received induction therapy with a different antibody/combination: alemtuzumab(C1H), Thymoglobulin(rATG), daclizumab(Dac), rATG+C1H, and rATG+Dac. CD4+ T-cells were suppressed by C1H and rATG+C1H, as well as by rATG and rATG+Dac but to a lesser extent. The effect lasted for 3 years at around 40% of baseline values. CD8+ T-cells showed a similar trend but had a more rapid recovery to baseline. CD19+ B-cells were effectively suppressed for 2 months by C1H and rATG+C1H, and abruptly returned to baseline afterwards; suppression by rATG(7 doses) was modest but lasted longer. A higher proportion of CD56+CD16+ Natural Killer cells in C1H treated patients suggested a relatively spared effect of C1H on this cell type. Low CD25+ T-cells by 5-dose Dac returned to baseline around 6 months, whereas rATG+C1H and rATG+Dac showed persistent effect. CD4+CD25hi T-cells were suppressed by both rATG+C1H and rATG+Dac, but the initial proportion of CD4+CD25hi T-cells among CD4+ T-cells and CD4+CD25hi/CD4+CD25lo ratio were significantly higher in rATG+C1H. Overall, with extensive and persistent lymphocyte suppression by a simple administration of agents, single-dose rATG+C1H induction can be an alternative in renal transplantation.
authors.affiliation: DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida 33136, USA. jsageshima@med.miami.edu
authors.forename: Junichiro
authors.initials: J
authors.lastname: Sageshima
authors.forename: Gaetano
authors.initials: G
authors.lastname: Ciancio
authors.forename: Giselle
authors.initials: G
authors.lastname: Guerra
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Gaynor
authors.forename: Deborah
authors.initials: D
authors.lastname: Cova
authors.forename: Alberto
authors.initials: A
authors.lastname: Zarak
authors.forename: Linda
authors.initials: L
authors.lastname: Chen
authors.forename: Adela
authors.initials: A
authors.lastname: Mattiazzi
authors.forename: Warren
authors.initials: W
authors.lastname: Kupin
authors.forename: David
authors.initials: D
authors.lastname: Roth
authors.forename: Lois
authors.initials: L
authors.lastname: Hanson
authors.forename: Alan S
authors.initials: AS
authors.lastname: Livingstone
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
authors.forename: George W
authors.initials: GW
authors.lastname: Burke
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000494:pharmacology*; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019002:CD56 Antigen / Q000096:biosynthesis; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000096:biosynthesis; D012189:Retrospective Studies; D060168:Thymocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D019002:CD56 Antigen; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D017452:Receptors, IgG; D000074323:Alemtuzumab; D000077561:Daclizumab; C512542:thymoglobulin