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Intrathecal IgM production is a strong risk factor for early conversion to multiple sclerosis.
Journal article

Intrathecal IgM production is a strong risk factor for early conversion to multiple sclerosis.

  • Pfuhl C From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Grittner U From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Gieß RM From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Scheel M From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Behrens JR From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Rasche L From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Pache FC From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Wenzel R From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Brandt AU From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Bellmann-Strobl J From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Paul F From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
  • Ruprecht K From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland. klemens.ruprecht@charite.de.
  • Oechtering J From the Department of Neurology (C.P., J.R.B., F.C.P., R.W., F.P., K.R., J.O.), NeuroCure Clinical Research Center (C.P., R.M.G., M.S., J.R.B., L.R., F.C.P., A.U.B., J.B.-S., F.P.), Institute for Biometry and Clinical Epidemiology (U.G.), and Department of Neuroradiology (M.S.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (U.G.), Berlin; Department of Neurology (A.U.B.), University of California Irvine; Experimental and Clinical Research Center (J.B.-S., F.P.), Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany; and Neurological Clinic and Policlinic (J.O.), Basel University Hospital, Basel, Switzerland.
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  • 2019-09-11
Published in:
  • Neurology. - 2019
Adult
Age of Onset
Aged
Demyelinating Diseases
Disease Progression
Female
Humans
Immunoglobulin G
Immunoglobulin M
Male
Middle Aged
Multiple Sclerosis
Oligoclonal Bands
Risk Factors
Severity of Illness Index
English OBJECTIVES
To evaluate intrathecal immunoglobulin M (IgM) production, as compared to previously established risk factors, as risk factor for conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to explore the association of intrathecal IgM production with onset age and radiologic and CSF findings in CIS/early MS.


METHODS
Comprehensive CSF data, including oligoclonal immunoglobulin G (IgG) bands (OCB) and calculated intrathecal IgM and IgG production, were collected in a prospective study of 150 patients with CIS/early MS with regular clinical and MRI assessments.


RESULTS
Intrathecal IgM production >0% occurred in 23.2% (33/142) of patients, who were on average 5 years younger at disease onset (p = 0.013) and more frequently had infratentorial lesions (18/32, 56.3%) than patients without intrathecal IgM production (33/104, 31.7%, p = 0.021). In multivariable Cox regression analyses, intrathecal IgM production in patients with a CIS (n = 93, median clinical and MRI follow-up 24 and 21 months) was strongly associated with conversion to MS according to the McDonald 2010 criteria (hazard ratio [95% confidence interval] 3.05 [1.45-6.44], p = 0.003) after adjustment for age (0.96 [0.93-1.00], p = 0.059), OCB (0.92 [0.33-2.61], p = 0.879), intrathecal IgG production (0.98 [0.48-1.99], p = 0.947), and radiologic evidence of dissemination in space (2.63 [1.11-6.22], p = 0.028).


CONCLUSION
Intrathecal IgM production is a strong independent risk factor for early conversion to MS and may thus represent a clinically meaningful marker for predicting future disease activity in patients with a CIS.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/135889
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