Identification of coronin-1a as a novel antibody target for clinically isolated syndrome and multiple sclerosis

Authors

  • Myrthe Rouwette,

    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
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  • Jean-Paul Noben,

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

    1. Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
    2. Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, 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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  • 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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  • Peter J. Jongen,

    1. MS4 Research Institute, Nijmegen, The Netherlands
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  • Marcel M. Verbeek,

    1. Departments of Neurology and Laboratory Medicine, Donders Centre for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands
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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 of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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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
    • Hasselt University, Biomedical Research Institute (BIOMED) and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
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Address correspondence and reprint requests to Dr. Veerle Somers, Hasselt University, Biomedical Research Institute, and Transnationale Universiteit Limburg, School of Life Sciences, Martelarenlaan 42, 3500 Hasselt, Belgium. E-mail: veerle.somers@uhasselt.be

Abstract

Recently, we identified the mimotope UH-CIS6 as a novel candidate antibody target for clinically isolated syndrome (CIS) and relapsing-remitting (RR) multiple sclerosis (MS). The purpose of this study was to further validate UH-CIS6 as an antibody target for CIS and MS and to identify the in vivo antibody target of UH-CIS6. First, a UH-CIS6 peptide ELISA was optimized. Next, we investigated the antibody response toward UH-CIS6 in cerebrospinal fluid (CSF) from patients with CIS (= 20), MS (= 43) and other neurological diseases (= 42). Immunoprecipitation of anti-UH-CIS6 antibodies on a normal human brain lysate was performed to identify the in vivo antibody target of UH-CIS6. The cellular expression of an in vivo candidate target was investigated by immunohistochemistry using MS brain tissue sections. Antibody reactivity toward UH-CIS6 was detected in a significantly increased proportion of CSF samples from CIS and RR-MS patients as compared with neurological controls (= 0.046). We identified and confirmed coronin-1a as the in vivo antibody target for UH-CIS6. Furthermore, coronin-1a was expressed by T cells and macrophages in an active MS lesion. Together, these results demonstrate that coronin-1a is a novel antibody target for CIS and MS.

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