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

Mult Scler. 2016 Jul;22(8):1048-60. doi: 10.1177/1352458515607651. Epub 2015 Oct 2.


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.

Keywords: CD62L; JCV index; L-selectin; Natalizumab; PML; risk stratification.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antibodies, Viral / blood*
  • Biomarkers / blood
  • Europe
  • Humans
  • Immunocompromised Host
  • JC Virus / immunology*
  • L-Selectin / blood*
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Leukoencephalopathy, Progressive Multifocal / immunology
  • Leukoencephalopathy, Progressive Multifocal / prevention & control
  • Leukoencephalopathy, Progressive Multifocal / virology
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Natalizumab / adverse effects*
  • Opportunistic Infections / chemically induced*
  • Opportunistic Infections / immunology
  • Opportunistic Infections / virology
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Serologic Tests
  • Treatment Outcome


  • Antibodies, Viral
  • Biomarkers
  • Natalizumab
  • SELL protein, human
  • L-Selectin