PML risk stratification using anti-JCV antibody index and L-selectin

Nicholas Schwab, Tilman Schneider-Hohendorf, Béatrice Pignolet, Michela Spadaro, Dennis Görlich, Ingrid Meinl, Susanne Windhagen, Björn Tackenberg, Johanna Breuer, Ester Cantó, Tania Kümpfel, Reinhard Hohlfeld, Volker Siffrin, Felix Luessi, Anita Posevitz-Fejfár, Xavier Montalban, Sven G. Meuth, Frauke Zipp, Ralf Gold, Renaud A. Du PasquierChristoph Kleinschnitz, Annett Jacobi, Manuel Comabella, Antonio Bertolotto, David Brassat, Heinz Wiendl

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46 Citations (Scopus)


© SAGE Publications. Background: 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. Objective: This study aimed at verifying and integrating both parameters into one algorithm for risk stratification. Methods: 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). Results: 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. Conclusions: 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.
Original languageEnglish
Pages (from-to)1048-1060
JournalMultiple Sclerosis
Issue number8
Publication statusPublished - 1 Jul 2016


  • CD62L
  • JCV index
  • L-selectin
  • Natalizumab
  • PML
  • risk stratification


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