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Title:

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

Document type:
Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
Author(s):
Schwab, Nicholas; Schneider-Hohendorf, Tilman; Posevitz, Vilmos; Breuer, Johanna; Göbel, Kerstin; Windhagen, Susanne; Brochet, Bruno; Vermersch, Patrick; Lebrun-Frenay, Christine; Posevitz-Fejfár, Anita; Capra, Ruggero; Imberti, Luisa; Straeten, Vera; Haas, Juergen; Wildemann, Brigitte; Havla, Joachim; Kümpfel, Tania; Meinl, Ingrid; Niessen, Kyle; Goelz, Susan; Kleinschnitz, Christoph; Warnke, Clemens; Buck, Dorothea; Gold, Ralf; Kieseier, Bernd C; Meuth, Sven G; Foley, John; Chan, Andrew; Brass...     »
Abstract:
To find biomarkers identifying patients at risk for the development of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment.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.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.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.
Journal title abbreviation:
Neurology
Year:
2013
Journal volume:
81
Journal issue:
10
Pages contribution:
865-71
Language:
eng
Fulltext / DOI:
doi:10.1212/WNL.0b013e3182a351fb
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/23925765
Print-ISSN:
0028-3878
TUM Institution:
Neurologische Klinik und Poliklinik
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