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

Authors

  • N. Schwab
  • T. Schneider-Hohendorf
  • B. Pignolet
  • M. Spadaro
  • D. Görlich
  • I. Meinl
  • S. Windhagen
  • B. Tackenberg
  • J. Breuer
  • E. Cantó
  • T. Kümpfel
  • R. Hohlfeld
  • V. Siffrin
  • F. Luessi
  • A. Posevitz-Fejfár
  • X. Montalban
  • S.G. Meuth
  • F. Zipp
  • R. Gold
  • R.A. Du Pasquier
  • C. Kleinschnitz
  • A. Jacobi
  • M. Comabella
  • A. Bertolotto
  • D. Brassat
  • H. Wiendl

Journal

  • Multiple Sclerosis Journal

Citation

  • Mult Scler J 22 (8): 1048-1060

Abstract

  • 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.


DOI

doi:10.1177/1352458515607651