title: Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia
creator: Jarius, Sven
creator: Scharf, Madeleine
creator: Begemann, Nora
creator: Stöcker, Winfried
creator: Probst, Christian
creator: Serysheva, Irina I.
creator: Nagel, Sigrun
creator: Graus, Francesc
creator: Psimaras, Dimitri
creator: Wildemann, Brigitte
creator: Komorowski, Lars
subject: ddc-570
subject: 570 Life sciences
subject: ddc-610
subject: 610 Medical sciences Medicine
description: We report on a serum autoantibody associated with cerebellar ataxia. Immunohistochemical studies of sera from four patients referred for autoantibody testing revealed binding of high-titer (up to 1:5,000) IgG antibodies, mainly IgG1, to the molecular layer, Purkinje cell layer, and white matter on mouse, rat, porcine, and monkey cerebellum sections. The antibody bound to PC somata, dendrites, and axons, resulting in a binding pattern similar to that reported for anti-Ca/anti-ARHGAP26, but did not react with recombinant ARHGAP26. Extensive control studies were performed to rule out a broad panel of previously described paraneoplastic and non-paraneoplastic anti-neural autoantibodies. The characteristic binding pattern as well as double staining experiments suggested inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) as the target antigen. Verification of the antigen included specific neutralization of the tissue reaction following preadsorption with ITPR1 (but not ARHGAP26) and a dot-blot assay with purified ITPR1 protein. By contrast, anti-ARHGAP26-positive sera did not bind to ITPR1. In a parallel approach, a combination of histoimmunoprecipitation and mass spectrometry also identified ITPR1 as the target antigen. Finally, a recombinant cell-based immunofluorescence assay using HEK293 cells expressing ITPR1 and ARHGAP26, respectively, confirmed the identification of ITPR1. Mutations of ITPR1 have previously been implicated in spinocerebellar ataxia with and without cognitive decline. Our findings suggest a role of autoimmunity against ITPR1 in the pathogenesis of autoimmune cerebellitis and extend the panel of diagnostic markers for this disease. 
publisher: BioMed Central
date: 2014
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/19352/1/12974_2014_Article_206.pdf
identifier: DOI:
identifier: urn:nbn:de:bsz:16-heidok-193524
identifier:   Jarius, Sven ; Scharf, Madeleine ; Begemann, Nora ; Stöcker, Winfried ; Probst, Christian ; Serysheva, Irina I. ; Nagel, Sigrun ; Graus, Francesc ; Psimaras, Dimitri ; Wildemann, Brigitte ; Komorowski, Lars  (2014) Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia.  Journal of neuroinflammation: JNI, 11 (206).  pp. 1-12.  ISSN 1742-2094     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/19352/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng