Prolonged lymphocyte depletion by single-dose rabbit anti-thymocyte globulin and alemtuzumab in kidney transplantation

Transpl Immunol. 2011 Sep;25(2-3):104-11. doi: 10.1016/j.trim.2011.07.002. Epub 2011 Jul 19.

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.

MeSH terms

  • Adult
  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Neoplasm / administration & dosage
  • Antibodies, Neoplasm / pharmacology*
  • Antilymphocyte Serum / administration & dosage
  • Antilymphocyte Serum / immunology
  • Antilymphocyte Serum / pharmacology*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD56 Antigen / biosynthesis
  • Daclizumab
  • Female
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Kidney Transplantation / immunology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Depletion / methods*
  • Male
  • Middle Aged
  • Receptors, IgG / biosynthesis
  • Retrospective Studies
  • Thymocytes / drug effects
  • Thymocytes / immunology

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Antilymphocyte Serum
  • CD56 Antigen
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, IgG
  • Alemtuzumab
  • Daclizumab
  • thymoglobulin