title: JC virus detection and JC virus-specific immunity in natalizumab-treated multiple sclerosis patients.
abstract: BACKGROUND
  The use of natalizumab in multiple sclerosis (MS) may favour JC virus reactivation; this phenomenon is usually asymptomatic but can, albeit rarely, evolve into frank progressive multifocal leucoencephalopathy (PML).
  
  
  METHODS
  JCV-specific CD8+ T lymphocytes were evaluated by flow cytometry over a 24-month period in 24 natalizumab-treated MS patients in whom JCV DNA was or was not detected in blood using quantitative real-time polymerase chain reaction; all these cases were asymptomatic.
  
  
  RESULTS
  Perforin- and grazymes-containing VP-1-specific CD8+ T lymphocytes were reduced whereas CD107a-expressing cells were increased in JCV positive patients, suggesting an active degranulation of these cells; naïve CD8+ T lymphocytes were also decreased whereas memory cells were increased in patients in whom JCV reactivation was observed.
  
  
  CONCLUSIONS
  The presence of a CD8+ T lymphocyte-mediated effector immune response offers a greater insight into reactivation of JCV and its clinical sequelae, and may help the monitoring of patients on natalizumab therapy.
authors.affiliation: Don C, Gnocchi Foundation, ONLUS, Milan, Italy. rmancuso@dongnocchi.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Mancuso
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.forename: Ambra
authors.initials: A
authors.lastname: Hernis
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.forename: Cristian
authors.initials: C
authors.lastname: Ricci
authors.forename: Simone
authors.initials: S
authors.lastname: Agostini
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007109:Immunity / Q000187:drug effects* / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects; D007577:JC Virus / Q000276:immunology* / Q000302:isolation & purification*; D008137:Longitudinal Studies; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D000069442:Natalizumab; D054353:Perforin / Q000378:metabolism; D013045:Species Specificity; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D036022:Capsid Proteins; D016207:Cytokines; D004279:DNA, Viral; D052118:Lysosomal-Associated Membrane Protein 1; D000069442:Natalizumab; C062481:VP1 protein, polyomavirus; D054353:Perforin; D053804:Granzymes