eprintid: 19352
rev_number: 17
eprint_status: archive
userid: 1589
dir: disk0/00/01/93/52
datestamp: 2015-11-25 10:39:09
lastmod: 2024-07-02 02:28:33
status_changed: 2015-11-25 10:39:09
type: article
metadata_visibility: show
creators_name: Jarius, Sven
creators_name: Scharf, Madeleine
creators_name: Begemann, Nora
creators_name: Stöcker, Winfried
creators_name: Probst, Christian
creators_name: Serysheva, Irina I.
creators_name: Nagel, Sigrun
creators_name: Graus, Francesc
creators_name: Psimaras, Dimitri
creators_name: Wildemann, Brigitte
creators_name: Komorowski, Lars
title: Antibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in cerebellar ataxia
subjects: ddc-570
subjects: ddc-610
divisions: i-911100
abstract: 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. 
date: 2014
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 165355634X
own_urn: urn:nbn:de:bsz:16-heidok-193524
language: eng
bibsort: JARIUSSVENANTIBODIES2014
full_text_status: public
publication: Journal of neuroinflammation: JNI
volume: 11
number: 206
place_of_pub: London
pagerange: 1-12
issn: 1742-2094
citation:   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     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19352/1/12974_2014_Article_206.pdf