Novel cerebrospinal fluid and serum autoantibody targets for clinically isolated syndrome

Authors

  • Myrthe Rouwette,

    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
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  • Klaartje Somers,

    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
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  • Cindy Govarts,

    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
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  • Peter P. De Deyn,

    1. Department of Neurology, Middelheim Hospital, Antwerp, Belgium
    2. Laboratory of Neurochemistry and Behaviour, Department of Biomedical Sciences, Institute Born Bunge, University of Antwerp, Antwerp, Belgium
    3. Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands
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  • Raymond Hupperts,

    1. School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
    2. Department of Neurology, Orbis Medical Center, Sittard, The Netherlands
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  • Bart Van Wijmeersch,

    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
    2. Multiple Sclerosis and Rehabilitation Center, Overpelt, Belgium
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  • Brigit A. De Jong,

    1. MS Centre Nijmegen (MSCN) and Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands
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  • Marcel M. Verbeek,

    1. Departments of Neurology and Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
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  • Vincent Van Pesch,

    1. Department of Neurology, Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium
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  • Christian Sindic,

    1. Department of Neurology, Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium
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  • Luisa M. Villar,

    1. Departments of Neurology and Immunology, Ramón y Cajal Hospital, Madrid, Spain
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  • José C. Álvarez-Cermeño,

    1. Departments of Neurology and Immunology, Ramón y Cajal Hospital, Madrid, Spain
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  • Piet Stinissen,

    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
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  • Veerle Somers

    Corresponding author
    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
    • Address correspondence and reprint requests to Dr Veerle Somers, Hasselt University, Biomedical Research Institute, and Transnationale Universiteit Limburg, School of Life Sciences, Agoralaan, Building C, 3590 Diepenbeek, Belgium. E-mail: veerle.somers@uhasselt.be

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Abstract

Limited information is available on the identity of antigens targeted by antibodies present in cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS). The aim of this study was to identify novel antigens for CIS and investigate their prognostic potential to predict conversion to multiple sclerosis (MS). We applied serological antigen selection (SAS) to identify antigens interacting with antibodies present in the pooled CSF from four CIS patients, who developed MS. Antibody reactivity towards CIS antigens identified by SAS was tested in CSF and serum from patients with CIS (= 123/= 108), MS (= 65/= 44), and other (inflammatory) neurological diseases (= 75/= 38) as well as in healthy control sera (= 44). Using SAS, a panel of six novel CIS candidate antigens was identified. CSF antibody reactivity was detected in both CIS and relapsing-remitting (RR) MS. Serum reactivity was significantly increased in CIS and RR-MS as compared with controls (= 0.03). For two antigens, the frequency of antibody-positive patients was higher in CIS patients who converted to MS as compared with CIS patients without conversion. We identified novel CIS antigens to which antibody reactivity was primarily detected in CIS and RR-MS as compared to controls. Possible prognostic potential could be demonstrated for two antigens.

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