Clinical, serological and genetic predictors of response to immunotherapy in anti-IgLON5 disease.

Autor:	Grüter T; Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany., Möllers FE; Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany., Tietz A; Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany., Dargvainiene J; Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany., Melzer N; Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Heidbreder A; Institute for Sleep Medicine and Neuromuscular Disorders, University Hospital Münster, Münster, Germany.; Department of Neurology, Medical University Innsbruck, Innsbruck, Austria., Strippel C; Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany., Kraft A; Department of Neurology, Martha-Maria Hospital Halle-Dölau, Halle-Dölau, Germany., Höftberger R; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria., Schöberl F; Department of Neurology, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany., Thaler FS; Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians-Universität Munich, Munich, Germany.; Biomedical Center (BMC), Medical Faculty, Ludwig-Maximilians-Universität Munich, Martinsried, Germany., Wickel J; Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, Germany., Chung HY; Section of Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, Germany., Seifert F; Department of Neurology, University Hospital Erlangen, Erlangen, Germany., Tschernatsch M; Department of Neurology, Justus Liebig University Gießen, Gießen, Germany., Nagel M; Department of Neurology, Hospital Osnabrück, Osnabrück, Germany., Lewerenz J; Department of Neurology, Ulm University, Ulm, Germany., Jarius S; Molecular Neuroimmunology Group, Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany., Wildemann BC; Molecular Neuroimmunology Group, Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany., de Azevedo L; Department of Neurology, Schön hospital Hamburg Eilbek, Hamburg, Germany., Heidenreich F; Department of Neurology, Diakovere Hospital Henriettenstift, Hannover, Germany., Heusgen R; Max Planck Institute for Psychiatry, Munich, Germany., Hofstadt-van Oy U; Department of Neurology, Knappschaftskrankenhaus Dortmund - Klinikum Westfalen, Dortmund, Germany., Linsa A; Department of Neurology, Seenland Hospital Lausitz, Hoyerswerda, Germany., Maaß JJ; Department of Neurology, Medius Hospital Kirchheim, Kirchheim, Germany., Menge T; Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.; Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Ringelstein M; Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.; Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany., Pedrosa DJ; Department of Neurology, University Hospital of Gießen and Marburg, Marburg, Germany., Schill J; Department of Neurology, Hospital Darmstadt, Darmstadt, Germany., Seifert-Held T; Department of Neurology, Medical University of Graz, Graz, Austria., Seitz C; Department of Neurology, Johannes Gutenberg University Mainz, Mainz, Germany., Tonner S; Department of Neurology, Saarland-Heilstätten, Hospital Merzig, Merzig, Germany., Urbanek C; Department of Neurology, Hospital Ludwigshafen, Ludwigshafen, Germany., Zittel S; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Markewitz R; Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany., Korporal-Kuhnke M; Molecular Neuroimmunology Group, Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany., Schmitter T; Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany., Finke C; Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany., Brüggemann N; Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany., Bien CI; Laboratory Krone, Bad Salzuflen, Germany., Kleiter I; Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.; Marianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany., Gold R; Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany., Wandinger KP; Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany.; Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany., Kuhlenbäumer G; Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany., Leypoldt F; Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany.; Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany., Ayzenberg I; Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.; I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2023 Feb 13; Vol. 146 (2), pp. 600-611.
DOI:	10.1093/brain/awac090
Abstrakt:	Anti-IgLON5 disease is a newly defined clinical entity characterized by a progressive course with high disability and mortality rate. While precise pathogenetic mechanisms remain unclear, features characteristic of both autoimmune and neurodegenerative diseases were reported. Data on immunotherapy are limited, and its efficacy remains controversial. In this study, we retrospectively investigated an anti-IgLON5 disease cohort with special focus on clinical, serological and genetic predictors of the immunotherapy response and long-term outcome. Patients were recruited from the GENERATE (German Network for Research on Autoimmune Encephalitis) registry. Along with clinical parameters, anti-IgLON5 immunoglobulin (Ig)G in serum and CSF, anti-IgLON5 IgG1-4, IgA and IgM in serum, neurofilament light chain and glial fibrillary acidic protein in serum as well as human leukocyte antigen-genotypes were determined. We identified 53 patients (symptom onset 63.8 ± 10.3 years, female:male 1:1.5). The most frequent initial clinical presentations were bulbar syndrome, hyperkinetic syndrome or isolated sleep disorder [at least one symptom present in 38% (20/53)]. At the time of diagnosis, the majority of patients had a generalized multi-systemic phenotype; nevertheless, 21% (11/53) still had an isolated brainstem syndrome and/or a characteristic sleep disorder only. About one third of patients [28% (15/53)] reported subacute disease onset and 51% (27/53) relapse-like exacerbations during the disease course. Inflammatory CSF changes were evident in 37% (19/51) and increased blood-CSF-barrier permeability in 46% (21/46). CSF cell count significantly decreased, while serum anti-IgLON5 IgG titre increased with disease duration. The presence of human leukocyte antigen-DRB1*10:01 [55% (24/44)] was associated with higher serum anti-IgLON5 IgG titres. Neurofilament light chain and glial fibrillary acidic protein in serum were substantially increased (71.1 ± 103.9 pg/ml and 126.7 ± 73.3 pg/ml, respectively). First-line immunotherapy of relapse-like acute-to-subacute exacerbation episodes resulted in improvement in 41% (11/27) of patients and early initiation within the first 6 weeks was a predictor for therapy response. Sixty-eight per cent (36/53) of patients were treated with long-term immunotherapy and 75% (27/36) of these experienced no further disease progression (observation period of 20.2 ± 15.4 months). Long-term immunotherapy initiation during the first year after onset and low pre-treatment neurofilament light chain were significant predictors for a better outcome. In conclusion, subacute disease onset and early inflammatory CSF changes support the primary role of autoimmune mechanisms at least at initial stages of anti-IgLON5 disease. Early immunotherapy, prior to advanced neurodegeneration, is associated with a better long-term clinical outcome. Low serum neurofilament light chain at treatment initiation may serve as a potential biomarker of the immunotherapy response. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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