Directly to content
  1. Publishing |
  2. Search |
  3. Browse |
  4. Recent items rss |
  5. Open Access |
  6. Jur. Issues |
  7. DeutschClear Cookie - decide language by browser settings

Inositol 1,4,5-trisphosphate receptor type 1 autoantibodies in paraneoplastic and non-paraneoplastic peripheral neuropathy

Jarius, Sven ; Ringelstein, Marius ; Haas, Jürgen ; Serysheva, Irina I. ; Komorowski, Lars ; Fechner, Kai ; Wandinger, Klaus-Peter ; Albrecht, Philipp ; Hefter, Harald ; Moser, Andreas ; Neuen-Jacob, Eva ; Hartung, Hans-Peter ; Wildemann, Brigitte ; Aktas, Orhan

In: Journal of Neuroinflammation, 13 (2016), Nr. 278. pp. 1-17. ISSN 1742-2094

[thumbnail of 12974_2016_Article_737.pdf]
Preview
PDF, English
Download (3MB) | Lizenz: Creative Commons LizenzvertragInositol 1,4,5-trisphosphate receptor type 1 autoantibodies in paraneoplastic and non-paraneoplastic peripheral neuropathy by Jarius, Sven ; Ringelstein, Marius ; Haas, Jürgen ; Serysheva, Irina I. ; Komorowski, Lars ; Fechner, Kai ; Wandinger, Klaus-Peter ; Albrecht, Philipp ; Hefter, Harald ; Moser, Andreas ; Neuen-Jacob, Eva ; Hartung, Hans-Peter ; Wildemann, Brigitte ; Aktas, Orhan underlies the terms of Creative Commons Attribution 3.0 Germany

Citation of documents: Please do not cite the URL that is displayed in your browser location input, instead use the DOI, URN or the persistent URL below, as we can guarantee their long-time accessibility.

Abstract

Background: Recently, we described a novel autoantibody, anti-Sj/ITPR1-IgG, that targets the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in patients with cerebellar ataxia. However, ITPR1 is expressed not only by Purkinje cells but also in the anterior horn of the spinal cord, in the substantia gelatinosa and in the motor, sensory (including the dorsal root ganglia) and autonomic peripheral nervous system, suggesting that the clinical spectrum associated with autoimmunity to ITPR1 may be broader than initially thought. Here we report on serum autoantibodies to ITPR1 (up to 1:15,000) in three patients with (radiculo)polyneuropathy, which in two cases was associated with cancer (ITPR1-expressing adenocarcinoma of the lung, multiple myeloma), suggesting a paraneoplastic aetiology. Methods: Serological and other immunological studies, and retrospective analysis of patient records. Results: The clinical findings comprised motor, sensory (including severe pain) and autonomic symptoms. While one patient presented with subacute symptoms mimicking Guillain-Barré syndrome (GBS), the symptoms progressed slowly in two other patients. Electrophysiology revealed delayed F waves; a decrease in motor and sensory action potentials and conduction velocities; delayed motor latencies; signs of denervation, indicating sensorimotor radiculopolyneuropathy of the mixed type; and no conduction blocks. ITPR1-IgG belonged to the complement-activating IgG1 subclass in the severely affected patient but exclusively to the IgG2 subclass in the two more mildly affected patients. Cerebrospinal fluid ITPR1-IgG was found to be of predominantly extrathecal origin. A 3H-thymidine-based proliferation assay confirmed the presence of ITPR1-reactive lymphocytes among peripheral blood mononuclear cells (PBMCs). Immunophenotypic profiling of PBMCs protein demonstrated predominant proliferation of B cells, CD4 T cells and CD8 memory T cells following stimulation with purified ITPR1 protein. Patient ITPR1-IgG bound both to peripheral nervous tissue and to lung tumour tissue. A nerve biopsy showed lymphocyte infiltration (including cytotoxic CD8 cells), oedema, marked axonal loss and myelin-positive macrophages, indicating florid inflammation. ITPR1-IgG serum titres declined following tumour removal, paralleled by clinical stabilization. Conclusions: Our findings expand the spectrum of clinical syndromes associated with ITPR1-IgG and suggest that autoimmunity to ITPR1 may underlie peripheral nervous system diseases (including GBS) in some patients and may be of paraneoplastic origin in a subset of cases.

Document type: Article
Journal or Publication Title: Journal of Neuroinflammation
Volume: 13
Number: 278
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 26 Oct 2016 12:59
Date: 2016
ISSN: 1742-2094
Page Range: pp. 1-17
Faculties / Institutes: Service facilities > Interdisziplinäres Zentrum für Neurowissenschaften
Medizinische Fakultät Heidelberg > Neurologische Universitätsklinik
DDC-classification: 610 Medical sciences Medicine
About | FAQ | Contact | Imprint |
OA-LogoDINI certificate 2013Logo der Open-Archives-Initiative