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

Nicholas Schwab, Tilman Schneider-Hohendorf, Vilmos Posevitz, Johanna Breuer, Kerstin Göbel, Susanne Windhagen, Bruno Brochet, Patrick Vermersch, Christine Lebrun-Frenay, Anita Posevitz-Fejfár, Ruggero Capra, Luisa Imberti, Vera Straeten, Juergen Haas, Brigitte Wildemann, Joachim Havla, Tania Kümpfel, Ingrid Meinl, Kyle Niessen, Susan GoelzChristoph Kleinschnitz, Clemens Warnke, Dorothea Buck, Ralf Gold, Bernd C. Kieseier, Sven G. Meuth, John Foley, Andrew Chan, David Brassat, Heinz Wiendl

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

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 5 10) and ageand sex-matched healthy donors (n 5 31). All flow cytometric assessments were done on previously cryopreserved, viable peripheral blood mononuclear cells. Results: The percentage of L-selectin-expressing CD41 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 5 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.

Original languageEnglish
Pages (from-to)865-871
Number of pages7
JournalNeurology
Volume81
Issue number10
DOIs
StatePublished - 3 Sep 2013
Externally publishedYes

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