title: Cytomegalovirus Immunity After Alemtuzumab Induction in Desensitized Kidney Transplant Patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Transplant Immunology Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA. 2 Comprehensive Transplant Center, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA.
authors.forename: Shili
authors.initials: S
authors.lastname: Ge
authors.forename: Artur
authors.initials: A
authors.lastname: Karasyov
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.forename: Anna
authors.initials: A
authors.lastname: Petrosyan
authors.forename: Darly
authors.initials: D
authors.lastname: Lovato
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.forename: Ashley
authors.initials: A
authors.lastname: Vo
authors.forename: Stan C
authors.initials: SC
authors.lastname: Jordan
authors.forename: Mieko
authors.initials: M
authors.lastname: Toyoda
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D003587:Cytomegalovirus / Q000187:drug effects* / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D009894:Opportunistic Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D000069283:Rituximab