L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients

Neurology. 2013 Sep 3;81(10):865-71. doi: 10.1212/WNL.0b013e3182a351fb. Epub 2013 Aug 7.


Objective: To find biomarkers identifying patients at risk for the development of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment.

Methods: Patients were recruited from 10 European and US cohorts. Of 289 patients with multiple sclerosis (MS), 224 had been treated with natalizumab (18-80 months), 21 received other immune-modulatory treatments, and 28 were untreated. We had access to samples from 16 natalizumab PML patients. Eight of these patients had given blood before the diagnosis of PML. We also analyzed non-natalizumab-treated patients who developed PML (n = 10) and age- and sex-matched healthy donors (n = 31). All flow cytometric assessments were done on previously cryopreserved, viable peripheral blood mononuclear cells.

Results: The percentage of l-selectin-expressing CD4+ T cells was significantly lower in patients treated long-term with natalizumab (40.2%) when compared with patients not receiving natalizumab treatment (47.2%; p = 0.016) or healthy controls (61.0%; p < 0.0001). An unusually low percentage (9-fold lower; 4.6%) was highly correlated with the risk of developing PML in the patient group with available pre-PML samples when compared with non-PML natalizumab-treated patients (p ≤ 0.0001). Samples were gathered between 4 and 26 months before PML diagnosis.

Conclusions: The cell-based assessment of the percentage of l-selectin-expressing CD4 T cells could provide an urgently needed biomarker for individual PML risk assessment.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers / blood
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cohort Studies
  • Humans
  • L-Selectin / blood*
  • Leukoencephalopathy, Progressive Multifocal / blood*
  • Leukoencephalopathy, Progressive Multifocal / diagnosis
  • Leukoencephalopathy, Progressive Multifocal / pathology
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / pathology
  • Natalizumab
  • Risk Factors
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Natalizumab
  • L-Selectin