Wunsch, Marie, Jabari, Samir, Voussen, Barbara, Enders, Michael, Srinivasan, Shanthi, Cossais, Francois, Wedel, Thilo ORCID: 0000-0002-8146-2711, Boettner, Martina, Schwarz, Anna, Weyer, Linda, Goecer, Oktay, Schroeter, Michael, Maeurer, Mathias, Woenckhaus, Matthias, Pollok, Karolin, Radbruch, Helena, Klotz, Luisa, Scholz, Claus-Juergen, Nickel, Joachim, Friebe, Andreas, Addicks, Klaus, Erguen, Sueleyman, Lehmann, Paul V. and Kuerten, Stefanie (2017). The enteric nervous system is a potential autoimmune target in multiple sclerosis. Acta Neuropathol., 134 (2). S. 281 - 296. NEW YORK: SPRINGER. ISSN 1432-0533

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Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) in young adults that has serious negative socioeconomic effects. In addition to symptoms caused by CNS pathology, the majority of MS patients frequently exhibit gastrointestinal dysfunction, which was previously either explained by the presence of spinal cord lesions or not directly linked to the autoimmune etiology of the disease. Here, we studied the enteric nervous system (ENS) in a B cell-and antibody-dependent mouse model of MS by immunohistochemistry and electron microscopy at different stages of the disease. ENS degeneration was evident prior to the development of CNS lesions and the onset of neurological deficits in mice. The pathology was antibody mediated and caused a significant decrease in gastrointestinal motility, which was associated with ENS gliosis and neuronal loss. We identified autoantibodies against four potential target antigens derived from enteric glia and/or neurons by immunoprecipitation and mass spectrometry. Antibodies against three of the target antigens were also present in the plasma of MS patients as confirmed by ELISA. The analysis of human colon resectates provided evidence of gliosis and ENS degeneration in MS patients compared to non-MS controls. For the first time, this study establishes a pathomechanistic link between the well-established autoimmune attack on the CNS and ENS pathology in MS, which might provide a paradigm shift in our current understanding of the immunopathogenesis of the disease with broad diagnostic and therapeutic implications.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wunsch, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jabari, SamirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voussen, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Enders, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Srinivasan, ShanthiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cossais, FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wedel, ThiloUNSPECIFIEDorcid.org/0000-0002-8146-2711UNSPECIFIED
Boettner, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weyer, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goecer, OktayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeter, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maeurer, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woenckhaus, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pollok, KarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radbruch, HelenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klotz, LuisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scholz, Claus-JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nickel, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friebe, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Addicks, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erguen, SueleymanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, Paul V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuerten, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-224467
DOI: 10.1007/s00401-017-1742-6
Journal or Publication Title: Acta Neuropathol.
Volume: 134
Number: 2
Page Range: S. 281 - 296
Date: 2017
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-0533
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GLIAL-CELLS; ENCEPHALOMYELITIS; PATHOLOGY; DYSFUNCTION; INDUCTION; DYNAMICS; BRAIN; EAEMultiple languages
Clinical Neurology; Neurosciences; PathologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22446

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