title: Cerebrospinal fluid JC virus antibody index for diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy.
abstract: OBJECTIVE
  Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV ) in the diagnosis of natalizumab-associated PML.
  
  
  METHODS
  AIJCV was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as published.
  
  
  RESULTS
  Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5.
  
  
  CONCLUSIONS
  Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML.
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Warnke
authors.forename: Gloria
authors.initials: G
authors.lastname: von Geldern
authors.forename: Philipp
authors.initials: P
authors.lastname: Markwerth
authors.forename: Thomas
authors.initials: T
authors.lastname: Dehmel
authors.forename: Robert
authors.initials: R
authors.lastname: Hoepner
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.forename: Mathias
authors.initials: M
authors.lastname: Mäurer
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
authors.forename: Florian
authors.initials: F
authors.lastname: Wegner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: Vera
authors.initials: V
authors.lastname: Straeten
authors.forename: Volker
authors.initials: V
authors.lastname: Limmroth
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
authors.forename: Derik
authors.initials: D
authors.lastname: Hermsen
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningson
authors.forename: Eugene
authors.initials: E
authors.lastname: Major
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
authors.forename: Ortwin
authors.initials: O
authors.lastname: Adams
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000914:Antibodies, Viral / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004279:DNA, Viral / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D007577:JC Virus / Q000378:metabolism*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000134:cerebrospinal fluid* / Q000139:chemically induced / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000188:drug therapy; D000069442:Natalizumab; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D015415:Biomarkers; D004279:DNA, Viral; D000069442:Natalizumab
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