title: The effect of plasma exchange on serum anti-JC virus antibodies.
abstract: OBJECTIVE
  Natalizumab, a highly effective treatment for multiple sclerosis (MS) and Crohn's disease, is associated with progressive multifocal leukoencephalopathy (PML). Upon suspicion or diagnosis of PML, plasma exchange (PLEX) is performed to remove natalizumab from the circulation, allowing immune reconstitution of the central nervous system. Since PLEX may also remove other circulating antibodies, we examined the effects of PLEX on serum immunoglobulin (IgG) and anti-JC virus (JCV) antibody levels in MS patients with and without PML.
  
  
  METHODS
  Serum samples from 12 natalizumab-treated patients without PML collected before, during and after PLEX were tested for IgG isotypes using a commercial assay, and for anti-JCV antibodies using a two-step enzyme-linked immunosorbent assay. Five natalizumab-treated PML patients who underwent PLEX were also tested for anti-JCV antibodies.
  
  
  RESULTS
  PLEX produced a two- to three-fold reduction in all IgG isotypes. Among patients without PML, 42% (five of 12 patients) had detectable anti-JCV antibodies before PLEX; in these patients, anti-JCV antibodies were reduced approximately two- to five-fold, with levels returning to 50-100 percent of baseline two weeks after the final PLEX. The five PML patients, all of whom had detectable anti-JCV antibodies before PLEX, experienced similar reductions in anti-JCV antibody levels following PLEX.
  
  
  CONCLUSIONS
  Our results indicate that PLEX effectively removes circulating antibodies; however, levels of endogenous anti-JCV antibody, unlike exogenously administered natalizumab, were replenished relatively quickly following PLEX. While interpretation of anti-JCV antibody levels during or within two weeks after PLEX may be problematic, humoral JCV immunity is not abolished by PLEX and antibody levels are rapidly restored.
authors.affiliation: Biogen Idec Inc., Cambridge, MA 02142, USA. meena.subramanyam@biogenidec.com
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanyam
authors.forename: Tatiana
authors.initials: T
authors.lastname: Plavina
authors.forename: Bhupendra O
authors.initials: BO
authors.lastname: Khatri
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.forename: Susan E
authors.initials: SE
authors.lastname: Goelz
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced / Q000175:diagnosis* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000628:therapy* / Q000821:virology*; D000069442:Natalizumab; D010951:Plasma Exchange / Q000009:adverse effects*; D027601:Polyomavirus Infections / Q000276:immunology; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D007155:Immunologic Factors; D000069442:Natalizumab