Neurochondrin is a neuronal target antigen in autoimmune cerebellar degeneration.
Ramona Miske,Catharina C. Gross,Madeleine Scharf,Kristin S. Golombeck,Marvin Hartwig,Urvashi Bhatia,Andreas Schulte-Mecklenbeck,Kathrin Bönte,Christine Strippel,Ludger Schöls,Matthis Synofzik,Hubertus Lohmann,Inga M Dettmann,Michael Deppe,Swantje Mindorf,Tobias Warnecke,Yvonne Denno,Bianca Teegen,Christian Probst,Stefanie Brakopp,Klaus-Peter Wandinger,Heinz Wiendl,Winfried Stöcker,Sven G. Meuth,Lars Komorowski,Nico Melzer +25 more
TLDR
No neurochondrin reactivity was found in control cohorts of various neural autoantibody-associated neurologic syndromes, relapsing-remitting multiple sclerosis, cerebellar type of multiple system atrophy, hereditary Cerebellar ataxias, other neurologic disorders, or healthy donors.Abstract:
Objective To report on a novel neuronal target antigen in 3 patients with autoimmune cerebellar degeneration. Methods Three patients with subacute to chronic cerebellar ataxia and controls underwent detailed clinical and neuropsychological assessment together with quantitative high-resolution structural MRI. Sera and CSF were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IFA) and immunoblot. Immunoprecipitation with lysates of hippocampus and cerebellum combined with mass spectrometric analysis was used to identify the autoantigen, which was verified by recombinant expression in HEK293 cells and use in several immunoassays. Multiparameter flow cytometry was performed on peripheral blood and CSF, and peripheral blood was subjected to T-cell receptor spectratyping. Results Patients presented with a subacute to chronic cerebellar and brainstem syndrome. MRI was consistent with cortical and cerebellar gray matter atrophy associated with subsequent neuroaxonal degeneration. IFA screening revealed strong immunoglobulin G1 reactivity in sera and CSF with hippocampal and cerebellar molecular and granular layers, but not with a panel of 30 recombinantly expressed established neural autoantigens. Neurochondrin was subsequently identified as the target antigen, verified by IFA and immunoblot with HEK293 cells expressing human neurochondrin as well as the ability of recombinant neurochondrin to neutralize the autoantibodies' tissue reaction. Immune phenotyping revealed intrathecal accumulation and activation of B and T cells during the acute but not chronic phase of the disease. T-cell receptor spectratyping suggested an antigen-specific T-cell response accompanying the formation of antineurochondrin autoantibodies. No such neurochondrin reactivity was found in control cohorts of various neural autoantibody-associated neurologic syndromes, relapsing-remitting multiple sclerosis, cerebellar type of multiple system atrophy, hereditary cerebellar ataxias, other neurologic disorders, or healthy donors. Conclusion Neurochondrin is a neuronal target antigen in autoimmune cerebellar degeneration.read more
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Autoantibodies in neurological disease
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Immune-mediated Cerebellar Ataxias: Practical Guidelines and Therapeutic Challenges
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Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications.
TL;DR: An immune scheme underlying this disabling disease is proposed and potential therapeutic strategies that could blunt this cerebellum-specific autoimmune disease are discussed.
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Neurochondrin neurological autoimmunity.
Shahar Shelly,Thomas J. Kryzer,Lars Komorowski,Ramona Miske,Mark Anderson,Eoin P. Flanagan,Shannon R. Hinson,Vanda A. Lennon,Sean J. Pittock,Andrew McKeon +9 more
TL;DR: In this series, neurochondrin autoimmunity was usually accompanied by a nonparaneoplastic rapidly progressive rhombencephalitis with poor neurologic outcomes, and other phenotypes and occasional paraneoplastics causes may occur.
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Neurochondrin Antibody Serum Positivity in Three Cases of Autoimmune Cerebellar Ataxia.
TL;DR: The NCDN antibody was positive in three male patients in whom the onset ages were four years and 11 months, two years and seven months and 67 years old, and early immunotherapy may have a beneficial impact on prognosis.
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