title: PML risk stratification using anti-JCV antibody index and L-selectin.
abstract: Natalizumab treatment is associated with progressive multifocal leukoencephalopathy (PML) development. Treatment duration, prior immunosuppressant use, and JCV serostatus are currently used for risk stratification, but PML incidence stays high. Anti-JCV antibody index and L-selectin (CD62L) have been proposed as additional risk stratification parameters.
  
  
  
  This study aimed at verifying and integrating both parameters into one algorithm for risk stratification.
  
  
  
  Multicentric, international cohorts of natalizumab-treated MS patients were assessed for JCV index (1921 control patients and nine pre-PML patients) and CD62L (1410 control patients and 17 pre-PML patients).
  
  
  
  CD62L values correlate with JCV serostatus, as well as JCV index values. Low CD62L in natalizumab-treated patients was confirmed and validated as a biomarker for PML risk with the risk factor "CD62L low" increasing a patient's relative risk 55-fold (p < 0.0001). Validation efforts established 86% sensitivity/91% specificity for CD62L and 100% sensitivity/59% specificity for JCV index as predictors of PML. Using both parameters identified 1.9% of natalizumab-treated patients in the reference center as the risk group.
  
  
  
  Both JCV index and CD62L have merit for risk stratification and share a potential biological relationship with implications for general PML etiology. A risk algorithm incorporating both biomarkers could strongly reduce PML incidence.
authors.affiliation: Department of Neurology, University of Münster, Germany nicholas.schwab@ukmuenster.de heinz.wiendl@ukmuenster.de.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schwab
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Schneider-Hohendorf
authors.affiliation: Pole des Neurosciences Centre Hospitalier Universitaire Toulouse, CPTP INSERM UMR 1043 et Université de Toulouse, UPS, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Pignolet
authors.affiliation: Clinical Neurobiology Unit, Regional Referring Multiple Sclerosis Centre (CRESM), Neuroscience Institute Cavalieri Ottolenghi (NICO), University Hospital San Luigi Gonzaga, Orbassano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Spadaro
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Münster, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Görlich
authors.affiliation: Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich and Munich Cluster Systems Neurology (SyNergy), Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meinl
authors.affiliation: Department of Neurology, Clinics Osnabrück, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Windhagen
authors.affiliation: Department of Neurology, Philipps University and University Clinics Gießen and Marburg, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Tackenberg
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Breuer
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Cantó
authors.affiliation: Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich and Munich Cluster Systems Neurology (SyNergy), Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.affiliation: Institute for Clinical Neuroimmunology, Ludwig-Maximilians-University Munich and Munich Cluster Systems Neurology (SyNergy), Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.affiliation: Department of Neurology, University of Mainz, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Siffrin
authors.affiliation: Department of Neurology, University of Mainz, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Luessi
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Posevitz-Fejfár
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Department of Neurology, University of Mainz, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
authors.affiliation: Department of Neurology, Ruhr University Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Divisions of Immunology and Allergy and of Neurology, Centre Hospitalier Universitaire Vaudois, Switzerland.
authors.forename: Renaud A
authors.initials: RA
authors.lastname: Du Pasquier
authors.affiliation: Department of Neurology, University of Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kleinschnitz
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Münster, Germany/Division of Rheumatology and Clinical Immunology, Brandenburg Medical School, Neuruppin, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Jacobi
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.affiliation: Clinical Neurobiology Unit, Regional Referring Multiple Sclerosis Centre (CRESM), Neuroscience Institute Cavalieri Ottolenghi (NICO), University Hospital San Luigi Gonzaga, Orbassano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
authors.affiliation: Pole des Neurosciences Centre Hospitalier Universitaire Toulouse, CPTP INSERM UMR 1043 et Université de Toulouse, UPS, France/David Brassat also represents the BioNAT study group.
authors.forename: David
authors.initials: D
authors.lastname: Brassat
authors.affiliation: Department of Neurology, University of Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D000465:Algorithms; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005060:Europe; D006801:Humans; D016867:Immunocompromised Host; D007577:JC Virus / Q000276:immunology*; D019041:L-Selectin / Q000097:blood*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab / Q000009:adverse effects*; D009894:Opportunistic Infections / Q000139:chemically induced* / Q000276:immunology / Q000821:virology; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012698:Serologic Tests; D016896:Treatment Outcome
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D000069442:Natalizumab; C546935:SELL protein, human; D019041:L-Selectin
keywords: CD62L; JCV index; L-selectin; Natalizumab; PML; risk stratification