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.
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.
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Databáze: MEDLINE
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