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
Citation Manager Formats
Make Comment
See Comments
Downloads
970
This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
No comments have been published for this article.
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Advertisement
Hemiplegic Migraine Associated With PRRT2 Variations A Clinical and Genetic Study
Dr. Robert Shapiro and Dr. Amynah Pradhan