title: Changes to anti-JCV antibody levels in a Swedish national MS cohort.
abstract: BACKGROUND
  The anti-JC virus (JCV) antibody status has been introduced to stratify patients with multiple sclerosis (MS) for higher or lower risk of progressive multifocal leukoencephalopathy (PML).
  
  
  OBJECTIVE
  To assess the potential utility of anti-JCV antibody levels for earlier diagnosis or prediction of PML.
  
  
  METHODS
  An analytically validated antibody assay was used to determine serological status, normalised optical density values, and dilution titres for anti-JCV antibodies. The method was applied to stored sera of 1157 patients with MS including five cases of PML, all enrolled in the Swedish pharmacovigilance study for natalizumab (NAT). Anticytomegalovirus (CMV) and antivaricella-zoster (VZV) antibody levels served as controls.
  
  
  RESULTS
  Prior to treatment with NAT, anti-JCV antibody levels were stable in the anti-JCV positive patients. During therapy, a slight decrease in anti-JCV and anti-VZV antibody levels, but not anti-CMV antibody levels, was observed. All five patients who developed PML showed a mild to moderate increase in anti-JCV antibody levels at time of PML diagnosis; pre-PML samples suggested that this increase might start already prior to diagnosis of PML.
  
  
  CONCLUSIONS
  Treatment initiation with NAT may lead to a slight decrease in anti-JCV and anti-VZV antibody levels, suggestive of a mild suppressive effect of NAT on antibody levels. Our findings in five cases of PML demonstrate that the onset of PML can be accompanied by increasing anti-JCV antibodies in serum. Monitoring of anti-JCV antibody levels could potentially be used as a tool for prediction or earlier diagnosis of PML during NAT treatment for MS. Further studies are warranted.
authors: Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, , Stockholm, Sweden.
authors: Clemens
authors: C
authors: Warnke
authors: Ryan
authors: R
authors: Ramanujam
authors: Tatiana
authors: T
authors: Plavina
authors: Tomas
authors: T
authors: Bergström
authors: Susan
authors: S
authors: Goelz
authors: Meena
authors: M
authors: Subramanyam
authors: Ingrid
authors: I
authors: Kockum
authors: Afsar
authors: A
authors: Rahbar
authors: Bernd C
authors: BC
authors: Kieseier
authors: Carolina
authors: C
authors: Holmén
authors: Tomas
authors: T
authors: Olsson
authors: Jan
authors: J
authors: Hillert
authors: Anna
authors: A
authors: Fogdell-Hahn
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood*; D003587:Cytomegalovirus / Q000276:immunology; D042241:Early Diagnosis; D005260:Female; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D000069442:Natalizumab; D060735:Pharmacovigilance; D011358:Product Surveillance, Postmarketing; D012307:Risk Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D000069442:Natalizumab; D007372:Interferons
keywords: INFECTIOUS DISEASES; MULTIPLE SCLEROSIS; NEUROVIROLOGY; VIROLOGY