title: JC polyomavirus viremia and progressive multifocal leukoencephalopathy in human leukocyte antigen-sensitized kidney transplant recipients desensitized with intravenous immunoglobulin and rituximab.
abstract: BACKGROUND
  Desensitization (DES) with intravenous immunoglobulin (IVIG) + rituximab is effective, safe, and increases the transplantation rate in human leukocyte antigen-sensitized patients. However, reports of progressive multifocal leukoencephalopathy (PML) caused by JC polyomavirus (JCPyV) in autoimmune patients treated with rituximab is concerning. Here, we report on the JCPyV viremia and PML status in kidney transplant patients with/without DES (non-DES).
  
  
  METHODS
  In total 1195 and 699 DNA samples from plasma in 117 DES (78% lymphocyte-depleting [LyD] induction) and 100 non-DES patients (45% LyD), respectively, were submitted for JCPyV-polymerase chain reaction. Results were compared in both groups.
  
  
  RESULTS
  No patients in either DES or non-DES developed PML or presented with any neurological symptoms. The JCPyV viremia rate was similar in DES and non-DES patients (3/117 vs. 9/100, P = 0.07). The JCPyV levels were low (median peak levels, 1025 copies/mL) and JCPyV viremia was observed only once during the study period in most patients. All 3 DES patients with JCPyV(+) received 1 dose rituximab and no DES patients with >1 dose rituximab showed JCPyV(+). All 3 JCPyV(+) DES patients received LyD induction, while only 2 of 9 JCPyV(+) non-DES patients did so, and the remaining 7 received non-LyD or no induction. JCPyV in leukocyte was mostly negative in DES and non-DES patients. Immunosuppression in patients with or without JCPyV(+) was similar. BK polyomavirus viremia was observed more commonly in patients with JCPyV(+) than in those without (P < 0.02).
  
  
  CONCLUSIONS
  Patients with IVIG + rituximab DES followed by transplantation with LyD induction and additional rituximab rarely show JCPyV viremia and appear at low risk for PML.
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Toyoda
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ahn
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kahwaji
authors.affiliation: Biostatistics Core, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mirocha
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Chu
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: A
authors.initials: A
authors.lastname: Vo
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: E
authors.initials: E
authors.lastname: Suviolahti
authors.affiliation: Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ge
authors.affiliation: Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Jordan
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007577:JC Virus; D016030:Kidney Transplantation / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology*; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000517:prevention & control; D000069283:Rituximab / Q000009:adverse effects / Q000494:pharmacology*; D014412:Tumor Virus Infections / Q000517:prevention & control; D014766:Viremia / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D016756:Immunoglobulins, Intravenous; D000069283:Rituximab
keywords: HLA-sensitized kidney transplant patients; JC polyomavirus; desensitization; progressive multifocal leukoencephalopathy; renal transplant; rituximab