title: Anti-JC virus antibodies: implications for PML risk stratification.
abstract: OBJECTIVE
  A study was undertaken to establish an enzyme-linked immunosorbent assay (ELISA) to detect JC virus (JCV)-specific antibodies in multiple sclerosis (MS) patients, and to evaluate its potential utility for identifying patients at higher or lower risk (ie, risk stratification) of developing progressive multifocal leukoencephalopathy (PML).
  
  
  METHODS
  A 2-step assay for detecting and confirming the presence of anti-JCV antibodies in human serum and plasma was developed and demonstrated to be both sensitive and specific. ELISA cutpoints were statistically established using sera from >800 MS patients from natalizumab clinical studies. Subsequently, this assay was used to determine the presence of anti-JCV antibodies in natalizumab-treated PML patients where serum samples were collected 16-180 months prior to the diagnosis of PML.
  
  
  RESULTS
  In our evaluation of natalizumab-treated MS patients, 53.6% tested positive for anti-JCV antibodies, with a 95% confidence interval of 49.9 to 57.3%. The false-negative rate of the ELISA was calculated to be approximately 2.5%, with an upper 1-sided confidence limit of 4.4%. Notably, we observed anti-JCV antibodies in all 17 available pre-PML sera samples, which was significantly different from the 53.6% seropositivity observed in the overall MS study population (p < 0.0001).
  
  
  CONCLUSIONS
  This 2-step assay provides a means to classify MS patients as having detectable or not detectable levels of anti-JCV antibodies. The finding that all 17 of the pre-PML samples that were available tested seropositive, and none tested seronegative, warrants further research on the clinical utility of the anti-JCV antibody assay as a potential tool for stratifying MS patients for higher or lower risk of developing PML.
authors.affiliation: Biogen Idec, Inc., Cambridge MA, USA.
authors.forename: Leonid
authors.initials: L
authors.lastname: Gorelik
authors.forename: Michaela
authors.initials: M
authors.lastname: Lerner
authors.forename: Sarah
authors.initials: S
authors.lastname: Bixler
authors.forename: Mary
authors.initials: M
authors.lastname: Crossman
authors.forename: Brian
authors.initials: B
authors.lastname: Schlain
authors.forename: Kenneth
authors.initials: K
authors.lastname: Simon
authors.forename: Amy
authors.initials: A
authors.lastname: Pace
authors.forename: Anne
authors.initials: A
authors.lastname: Cheung
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Chen
authors.forename: Melissa
authors.initials: M
authors.lastname: Berman
authors.forename: Fairuz
authors.initials: F
authors.lastname: Zein
authors.forename: Ewa
authors.initials: E
authors.lastname: Wilson
authors.forename: Ted
authors.initials: T
authors.lastname: Yednock
authors.forename: Alfred
authors.initials: A
authors.lastname: Sandrock
authors.forename: Susan E
authors.initials: SE
authors.lastname: Goelz
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanyam
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D004279:DNA, Viral / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis / Q000276:immunology / Q000628:therapy; D000069442:Natalizumab; D012307:Risk Factors; D019562:Viral Load / Q000379:methods
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004279:DNA, Viral; D000069442:Natalizumab