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 Goebel; Susanne Windhagen; Bruno Brochet; Patrick Vermersch; Christine Lebrun-Frenay; Anita Posevitz-Fejfar; Ruggero Capra; Luisa Imberti; Vera Straeten; Juergen Haas; Brigitte Wildemann; Joachim Havla; Tania Kuempfel; Ingrid Meinl; Kyle Niessen; Susan Goelz; Christoph Kleinschnitz; Clemens Warnke; Dorothea Buck; Ralf Gold; Bernd C. Kieseier; Sven G. Meuth; John Foley; Andrew Chan; David Brassat; Heinz Wiendl

doi:10.1212/WNL.0b013e3182a351fb

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 Goebel, Susanne Windhagen, Bruno Brochet, Patrick Vermersch, Christine Lebrun-Frenay, Anita Posevitz-Fejfar, Ruggero Capra, Luisa Imberti, Vera Straeten, Juergen Haas, Brigitte Wildemann, Joachim Havla, Tania Kuempfel, 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	865-871
Journal	Neurology
Volume	81
Issue number	10
DOIs	https://doi.org/10.1212/WNL.0b013e3182a351fb
Publication status	Published - 3 Sept 2013

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10.1212/WNL.0b013e3182a351fb

Cite this

Schwab, N., Schneider-Hohendorf, T., Posevitz, V., Breuer, J., Goebel, K., Windhagen, S., Brochet, B., Vermersch, P., Lebrun-Frenay, C., Posevitz-Fejfar, A., Capra, R., Imberti, L., Straeten, V., Haas, J., Wildemann, B., Havla, J., Kuempfel, T., Meinl, I., Niessen, K., ... Wiendl, H. (2013). L-Selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients. Neurology, 81(10), 865-871. https://doi.org/10.1212/WNL.0b013e3182a351fb

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

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.",

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

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doi = "10.1212/WNL.0b013e3182a351fb",

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Schwab, N, Schneider-Hohendorf, T, Posevitz, V, Breuer, J, Goebel, K, Windhagen, S, Brochet, B, Vermersch, P, Lebrun-Frenay, C, Posevitz-Fejfar, A, Capra, R, Imberti, L, Straeten, V, Haas, J, Wildemann, B, Havla, J, Kuempfel, T, Meinl, I, Niessen, K, Goelz, S, Kleinschnitz, C, Warnke, C, Buck, D, Gold, R, Kieseier, BC, Meuth, SG, Foley, J, Chan, A, Brassat, D & Wiendl, H 2013, 'L-Selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients', Neurology, vol. 81, no. 10, pp. 865-871. https://doi.org/10.1212/WNL.0b013e3182a351fb

TY - JOUR

T1 - L-Selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients

AU - Schwab, Nicholas

AU - Schneider-Hohendorf, Tilman

AU - Posevitz, Vilmos

AU - Breuer, Johanna

AU - Goebel, Kerstin

AU - Windhagen, Susanne

AU - Brochet, Bruno

AU - Vermersch, Patrick

AU - Lebrun-Frenay, Christine

AU - Posevitz-Fejfar, Anita

AU - Capra, Ruggero

AU - Imberti, Luisa

AU - Straeten, Vera

AU - Haas, Juergen

AU - Wildemann, Brigitte

AU - Havla, Joachim

AU - Kuempfel, Tania

AU - Meinl, Ingrid

AU - Niessen, Kyle

AU - Goelz, Susan

AU - Kleinschnitz, Christoph

AU - Warnke, Clemens

AU - Buck, Dorothea

AU - Gold, Ralf

AU - Kieseier, Bernd C.

AU - Meuth, Sven G.

AU - Foley, John

AU - Chan, Andrew

AU - Brassat, David

AU - Wiendl, Heinz

PY - 2013/9/3

Y1 - 2013/9/3

N2 - 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.

AB - 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.

U2 - 10.1212/WNL.0b013e3182a351fb

DO - 10.1212/WNL.0b013e3182a351fb

M3 - Article

C2 - 23925765

SN - 0028-3878

VL - 81

SP - 865

EP - 871

JO - Neurology

JF - Neurology

IS - 10

ER -