Cytomegalovirus Immunity After Alemtuzumab Induction in Desensitized Kidney Transplant Patients

Transplantation. 2017 Jul;101(7):1720-1726. doi: 10.1097/TP.0000000000001573.

Abstract

Background: Desensitization with IVIG + rituximab combined with alemtuzumab induction gives HLA-sensitized patients an opportunity for successful kidney transplantation. However, it may be associated with a high risk for viral infections due to combined T cell and B cell depletion.

Methods: Anti-cytomegalovirus (CMV) activity was assessed in 280 pretransplant and posttransplant blood samples from 33 desensitized patients who received alemtuzumab induction. CMV-specific CD8+ (CMV-Tc), CD4+ (CMV-Th) T cell activity, and natural killer (NK) cell number were measured by flow cytometry. Anti-CMV IgG was measured by enzyme-linked immunosorbent assay, and CMV DNA by polymerase chain reaction.

Results: All 30 CMV sero (+) patients were (+) for CMV-Tc and/or Th predesensitization, while 3 sero (-) patients showed no CMV-T cell activity. CMV-Tc and/or Th became (-) in 50% to 70% of these sero (+) patients at 1 month post-alemtuzumab. However, 75% showed CMV-T cell (+) by 2 months and 95% did so by 3 months post-alemtuzumab. More than 50% of pretranslpant NK cell levels were detected post-alemtuzumab. Anti-CMV IgG levels did not decrease posttransplant in sero (+) patients. Four patients developed CMV viremia with clearance by 1.2 months, which correlated with an increase or appearance of CMV-T cells, even in the sero (-) patient.

Conclusions: CMV-T cell activity, anti-CMV IgG, and NK cell-mediated antibody-dependent cell cytotoxicity were present in aleumtuzumab-treated CMV sero (+) patients. One sero (-) patient developed CMV-T cell responses post-CMV viremia. These results suggest that the IVIG + rituximab desensitization combined with alemtuzmab induction with triple immunosuppression maintenance does not result in prolonged suppression of anti-CMV immunity or increased risk for CMV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antibodies, Viral / blood
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • Desensitization, Immunologic / adverse effects
  • Desensitization, Immunologic / methods*
  • Female
  • Humans
  • Immunocompromised Host*
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Male
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / immunology*
  • Opportunistic Infections / virology
  • Risk Assessment
  • Risk Factors
  • Rituximab / therapeutic use
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Viral
  • Immunoglobulins, Intravenous
  • Immunosuppressive Agents
  • Alemtuzumab
  • Rituximab