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Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u223cDQB1*05:01, supports an autoimmune basis.<\/jats:p>\n                  <jats:p>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\u223cDQB1*05:01, HLA-DQA1*01:01\u223cDQB1*05:01 and HLA-DQA1*01:04\u223cDQB1*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\u2005years, 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\u223cDQB1*05:01.<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1093\/brain\/awae048","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T03:35:03Z","timestamp":1709264103000},"page":"2579-2592","source":"Crossref","is-referenced-by-count":47,"title":["HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4221-7131","authenticated-orcid":false,"given":"Selina M","family":"Yogeshwar","sequence":"first","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]},{"name":"Department of Neurology and Experimental Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t Berlin , 10117, Berlin ,","place":["Germany"]},{"name":"Einstein Center for Neurosciences Berlin, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mu\u00f1iz-Castrillo","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Sabater","sequence":"additional","affiliation":[{"name":"Neuroimmunology Program, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer, Caixa Research Institute, Universitat de Barcelona , 08036, Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Peris-Sempere","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamsee","family":"Mallajosyula","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Luo","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yan","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Yu","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia","family":"Fagundes 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,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Rogemond","sequence":"additional","affiliation":[{"name":"French Reference Center on Paraneoplastic Neurological Syndrome and Autoimmune Encephalitis, Hospices Civils de Lyon , 69677, Lyon ,","place":["France"]},{"name":"Institut MeLiS INSERM U1314\/CNRS UMR 5284, Universit\u00e9 Claude Bernard Lyon 1 , 69372 Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Laurie","family":"Pinto","sequence":"additional","affiliation":[{"name":"French Reference Center on Paraneoplastic Neurological Syndrome and Autoimmune Encephalitis, Hospices Civils de Lyon , 69677, Lyon ,","place":["France"]},{"name":"Institut MeLiS INSERM U1314\/CNRS UMR 5284, Universit\u00e9 Claude Bernard Lyon 1 , 69372 Lyon 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,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Dalmau","sequence":"additional","affiliation":[{"name":"Neurology Service, Hospital Cl\u00ednic of Barcelona, Biomedical Research Institute (IDIBAPS) , 08036 Barcelona ,","place":["Spain"]},{"name":"Catalan Institution for Research and Advanced Studies (ICREA) , 08010 Barcelona ,","place":["Spain"]},{"name":"Department of Neurology, University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]},{"name":"Spanish National Network for Research on Rare Diseases (CIBERER) , 28029 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Santamaria","sequence":"additional","affiliation":[{"name":"Neurology Service, Hospital Cl\u00ednic of Barcelona, Biomedical Research Institute (IDIBAPS) , 08036 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3306-8365","authenticated-orcid":false,"given":"Alex","family":"Iranzo","sequence":"additional","affiliation":[{"name":"Neurology Service, Hospital Cl\u00ednic of Barcelona, Biomedical Research Institute (IDIBAPS) , 08036 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Zurich , 8091 Zurich ,","place":["Switzerland"]},{"name":"Institute of Experimental Immunology, University of Zurich , 8057 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Giannoccaro","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica , 40139 Bologna ,","place":["Italy"]},{"name":"Dipartimento di Scienze Biomediche e Neuromotorie, Universit\u00e0 di Bologna , 40100 Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Liguori","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica , 40139 Bologna ,","place":["Italy"]},{"name":"Dipartimento di Scienze Biomediche e Neuromotorie, Universit\u00e0 di Bologna , 40100 Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Shimohata","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gifu University Graduate School of Medicine , 501-1194 Gifu ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gifu University Graduate School of Medicine , 501-1194 Gifu ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoya","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gifu University Graduate School of Medicine , 501-1194 Gifu ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Binks","sequence":"additional","affiliation":[{"name":"Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Department of Neurology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mariotto","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona , 37124 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-4792","authenticated-orcid":false,"given":"Alessandro","family":"Dinoto","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona , 37124 Verona ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bonello","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Walton Centre NHS Foundation Trust , L9 7LJ, Liverpool ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf , 40225 D\u00fcsseldorf ,","place":["Germany"]},{"name":"Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf , 40225 D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Tambasco","sequence":"additional","affiliation":[{"name":"Movement Disorders Center, Neurology Department, Perugia General Hospital and University of Perugia , 06156 Perugia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Nigro","sequence":"additional","affiliation":[{"name":"Movement Disorders Center, Neurology Department, Perugia General Hospital and University of Perugia , 06156 Perugia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Pr\u00fcss","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t Berlin , 10117, Berlin ,","place":["Germany"]},{"name":"German Center for Neurodegenerative Diseases (DZNE) Berlin , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"McKeon","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]},{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M","family":"Davis","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]},{"name":"Howard Hughes Medical Institute, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-9748","authenticated-orcid":false,"given":"Sarosh R","family":"Irani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital , Oxford OX3 9DU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4721-5952","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Honnorat","sequence":"additional","affiliation":[{"name":"French Reference Center on Paraneoplastic Neurological Syndrome and Autoimmune Encephalitis, Hospices Civils de Lyon , 69677, Lyon ,","place":["France"]},{"name":"Institut MeLiS INSERM U1314\/CNRS UMR 5284, Universit\u00e9 Claude Bernard Lyon 1 , 69372 Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carles","family":"Gaig","sequence":"additional","affiliation":[{"name":"Neurology Service, Hospital Cl\u00ednic of Barcelona, Biomedical Research Institute (IDIBAPS) , 08036 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7665-1171","authenticated-orcid":false,"given":"Carsten","family":"Finke","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t Berlin , 10117, Berlin ,","place":["Germany"]},{"name":"Berlin Center for Advanced Neuroimaging, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6928-5310","authenticated-orcid":false,"given":"Emmanuel","family":"Mignot","sequence":"additional","affiliation":[{"name":"Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,1]]},"reference":[{"key":"2025030422291767900_awae048-B1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S1474-4422(14)70051-1","article-title":"A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: A case series, characterisation of the antigen, and post-mortem study","volume":"13","author":"Sabater","year":"2014","journal-title":"Lancet 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