HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease.
Autor: | Yogeshwar SM; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, 10117, Berlin, Germany.; Einstein Center for Neurosciences Berlin, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany., Muñiz-Castrillo S; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Sabater L; Neuroimmunology Program, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Caixa Research Institute, Universitat de Barcelona, 08036, Barcelona, Spain., Peris-Sempere V; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Mallajosyula V; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA., Luo G; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Yan H; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Yu E; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Zhang J; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Lin L; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Fagundes Bueno F; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Ji X; Human Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA., Picard G; French Reference Center on Paraneoplastic Neurological Syndrome and Autoimmune Encephalitis, Hospices Civils de Lyon, 69677, Lyon, France.; Institut MeLiS INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1, 69372 Lyon, France., Rogemond V; French Reference Center on Paraneoplastic Neurological Syndrome and Autoimmune Encephalitis, Hospices Civils de Lyon, 69677, Lyon, France.; Institut MeLiS INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1, 69372 Lyon, France., Pinto AL; French Reference Center on Paraneoplastic Neurological Syndrome and Autoimmune Encephalitis, Hospices Civils de Lyon, 69677, Lyon, France.; Institut MeLiS INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1, 69372 Lyon, France., Heidbreder A; Kepler University Hospital, Department of Neurology, Johannes Kepler University, 4020 Linz, Austria., Höftberger R; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria., Graus F; Neurology Service, Hospital Clínic of Barcelona, Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain., Dalmau J; Neurology Service, Hospital Clínic of Barcelona, Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain.; Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.; Spanish National Network for Research on Rare Diseases (CIBERER), 28029 Madrid, Spain., Santamaria J; Neurology Service, Hospital Clínic of Barcelona, Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain., Iranzo A; Neurology Service, Hospital Clínic of Barcelona, Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain., Schreiner B; Department of Neurology, University Hospital Zurich, 8091 Zurich, Switzerland.; Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland., Giannoccaro MP; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, 40139 Bologna, Italy.; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, 40100 Bologna, Italy., Liguori R; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, 40139 Bologna, Italy.; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, 40100 Bologna, Italy., Shimohata T; Department of Neurology, Gifu University Graduate School of Medicine, 501-1194 Gifu, Japan., Kimura A; Department of Neurology, Gifu University Graduate School of Medicine, 501-1194 Gifu, Japan., Ono Y; Department of Neurology, Gifu University Graduate School of Medicine, 501-1194 Gifu, Japan., Binks S; Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.; Department of Neurology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU, UK., Mariotto S; Neurology Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, 37124 Verona, Italy., Dinoto A; Neurology Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, 37124 Verona, Italy., Bonello M; Department of Neurology, The Walton Centre NHS Foundation Trust, L9 7LJ, Liverpool, UK., Hartmann CJ; Department of Neurology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany., Tambasco N; Movement Disorders Center, Neurology Department, Perugia General Hospital and University of Perugia, 06156 Perugia, Italy., Nigro P; Movement Disorders Center, Neurology Department, Perugia General Hospital and University of Perugia, 06156 Perugia, Italy., Prüss H; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, 10117, Berlin, Germany.; German Center for Neurodegenerative Diseases (DZNE) Berlin, 10117 Berlin, Germany., McKeon A; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA., Davis MM; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA., Irani SR; Department of Neurology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU, UK., Honnorat J; French Reference Center on Paraneoplastic Neurological Syndrome and Autoimmune Encephalitis, Hospices Civils de Lyon, 69677, Lyon, France.; Institut MeLiS INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1, 69372 Lyon, France., Gaig C; Neurology Service, Hospital Clínic of Barcelona, Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain., Finke C; Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin, 10117, Berlin, Germany.; Berlin Center for Advanced Neuroimaging, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany., Mignot E; Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. |
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Jazyk: | angličtina |
Zdroj: | Brain : a journal of neurology [Brain] 2024 Jul 05; Vol. 147 (7), pp. 2579-2592. |
DOI: | 10.1093/brain/awae048 |
Abstrakt: | Anti-IgLON5 disease is a rare and likely underdiagnosed subtype of autoimmune encephalitis. The disease displays a heterogeneous phenotype that includes sleep, movement and bulbar-associated dysfunction. The presence of IgLON5-antibodies in CSF/serum, together with a strong association with HLA-DRB1*10:01∼DQB1*05:01, supports an autoimmune basis. In this study, a multicentric human leukocyte antigen (HLA) study of 87 anti-IgLON5 patients revealed a stronger association with HLA-DQ than HLA-DR. Specifically, we identified a predisposing rank-wise association with HLA-DQA1*01:05∼DQB1*05:01, HLA-DQA1*01:01∼DQB1*05:01 and HLA-DQA1*01:04∼DQB1*05:03 in 85% of patients. HLA sequences and binding cores for these three DQ heterodimers were similar, unlike those of linked DRB1 alleles, supporting a causal link to HLA-DQ. This association was further reflected in an increasingly later age of onset across each genotype group, with a delay of up to 11 years, while HLA-DQ-dosage dependent effects were also suggested by reduced risk in the presence of non-predisposing DQ1 alleles. The functional relevance of the observed HLA-DQ molecules was studied with competition binding assays. These proof-of-concept experiments revealed preferential binding of IgLON5 in a post-translationally modified, but not native, state to all three risk-associated HLA-DQ receptors. Further, a deamidated peptide from the Ig2-domain of IgLON5 activated T cells in two patients, compared with one control carrying HLA-DQA1*01:05∼DQB1*05:01. Taken together, these data support a HLA-DQ-mediated T-cell response to IgLON5 as a potentially key step in the initiation of autoimmunity in this disease. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.) |
Databáze: | MEDLINE |
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