September 03, 2013; 81 (10) Article
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 Goelz, Christoph Kleinschnitz, Clemens Warnke, Dorothea Buck, Ralf Gold, Bernd C. Kieseier, Sven G. Meuth, John Foley, Andrew Chan, David Brassat, Heinz Wiendl
First published August 7, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182a351fb
Nicholas Schwab
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Tilman Schneider-Hohendorf
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Vilmos Posevitz
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Johanna Breuer
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Kerstin Göbel
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Susanne Windhagen
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Bruno Brochet
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Patrick Vermersch
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Christine Lebrun-Frenay
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Anita Posevitz-Fejfár
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Ruggero Capra
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Luisa Imberti
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Vera Straeten
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Juergen Haas
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Brigitte Wildemann
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Joachim Havla
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Tania Kümpfel
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Ingrid Meinl
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Kyle Niessen
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Susan Goelz
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Christoph Kleinschnitz
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Clemens Warnke
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Dorothea Buck
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Ralf Gold
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Bernd C. Kieseier
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Sven G. Meuth
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
John Foley
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Andrew Chan
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
David Brassat
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
Heinz Wiendl
From the Department of Neurology (N.S., T.S.-H., V.P., J.B., K.G., A.P.-F., S.G.M., H.W.), University of Münster; Department of Neurology (S.W.), Clinics Osnabrück, Germany; Department of Neurology and INSERM U1049 (B.B.), University Bordeaux; Department of Neurology (P.V.), University Lille Nord de France; Department of Neurology (C.L.-F.), University of Nice Medical Centre, France; Multiple Sclerosis Center (R.C.) and Diagnostics Department (L.I.), Spedali Civili di Brescia, Montichiari, Italy; Department of Neurology (V.S.), Johannes-Wesling Clinic Minden; Department of Neurology (J. Haas, B.W., I.M.), Division of Molecular Neuroimmunology, University of Heidelberg; Institute of Clinical Neuroimmunology (J. Halva, T.K.), Ludwig-Maximilians-University, Munich, Germany; Elan Pharmaceuticals (K.N., S.G.), South San Francisco, CA; Department of Neurology (C.K.), University Clinic of Würzburg; Department of Neurology (C.W., B.C.K.), University of Düsseldorf; Department of Neurology (D. Buck), Technische Universität München, Munich; Department of Neurology (R.G., A.C.), St. Josef Hospital, Ruhr University, Bochum, Germany; Rocky Mountain Multiple Sclerosis Clinic (J.F.), Salt Lake City, UT; and UMR1043 and Pole des Neurosciences CHU Toulouse (D. Brassat), University of Toulouse, France.
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 Goelz, Christoph Kleinschnitz, Clemens Warnke, Dorothea Buck, Ralf Gold, Bernd C. Kieseier, Sven G. Meuth, John Foley, Andrew Chan, David Brassat, Heinz Wiendl
Neurology Sep 2013, 81 (10) 865-871; DOI: 10.1212/WNL.0b013e3182a351fb
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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 = 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.
GLOSSARY
- EDTA=
- ethylenediaminetetraacetic acid;
- JCV=
- JC virus;
- PBMC=
- peripheral blood mononuclear cells;
- PML=
- progressive multifocal leukoencephalopathy;
- RRMS=
- relapsing-remitting multiple sclerosis
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
Editorial, page 858
- Received January 6, 2013.
- Accepted in final form April 24, 2013.
- © 2013 American Academy of Neurology
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