Τίτλος:
Antibodies to inositol 1,4,5-triphosphate receptor 1 in patients with cerebellar disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective: To describe newly identified autoantibodies associated with cerebellar disorders. Design/Methods: We first screened the sera of 15 patients with cerebellar ataxia, without any known associated autoantibodies, with immunocytochemistry on mouse brain. After characterization and validation of a newly identified antibody, 85 additional patients with suspected autoimmune cerebellar disease were screened using a cell-based assay. Results: Immunoglobulin G from one of the first 15 patients demonstrated a distinct staining pattern on Purkinje neurons. This autoantibody, as characterized further by immunoprecipitation and mass spectrometry, was binding inositol 1,4,5-triphosphate receptor 1 (IP3R1), an intracellular channel that mediates the release of Ca2+ from intracellular stores. Anti-IP3R1 specificity was then validated with a cell-based assay. On this basis, screening of 85 other patients with cerebellar disease revealed 2 additional IP3R1-positive patients. All 3 patients presented with cerebellar ataxia; the first was eventually diagnosed with primary progressive multiple sclerosis, the second had a homozygous CAG insertion at the gene TBP, and the third was thought to have a neurodegenerative disease. Conclusions: We independently identified an autoantibody against IP3R1, a protein highly expressed in Purkinje neurons, confirming an earlier report. Because a mouse knockout model for IP3R1 exhibits ataxia and epilepsy, this autoantibody may have a functional role. The heterogeneity of the antibody-positive patients suggests that this antibody may either have a direct involvement in disease pathogenesis or it is a surrogate marker secondary to cerebellar injury. Anti-IP3R1 antibodies should be further explored in various ataxic and epileptic syndromes as they may denote a marker of response to immunotherapies. Copyright © 2016 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Συγγραφείς:
Fouka, P.
Alexopoulos, H.
Chatzi, I.
Dedos, S.G.
Samiotaki, M.
Panayotou, G.
Politis, P.
Tzioufas, A.
Dalakas, M.C.
Περιοδικό:
Neurology® Neuroimmunology and Neuroinflammation
Εκδότης:
Lippincott Williams and Wilkins
Λέξεις-κλειδιά:
autoantibody; immunoglobulin G; inositol 1,4,5 trisphosphate receptor; inositol 1,4,5 trisphosphate receptor 1; unclassified drug, animal tissue; antibody detection; Article; autoimmunity; calcium transport; cerebellar ataxia; cerebellum disease; controlled study; gene insertion; gene mutation; human; human cell; immunocytochemistry; immunoprecipitation; major clinical study; mass spectrometry; mouse; multiple sclerosis; nonhuman; Purkinje cell; receptor binding; staining
DOI:
10.1212/NXI.0000000000000306
