{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:04:46Z","timestamp":1787097886736,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Genetic factors predisposing to late\u2010onset myasthenia gravis (LOMG) have not been clearly defined yet. However, genome\u2010wide association studies identified Human Leukocyte Antigen (HLA) Class II alleles as a hotspot in this disease subtype. The aim of this study was to analyze the correlations of HLA Class II alleles with clinical data and titin antibodies in this patient subgroup.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study consecutively enrolled anti\u2010acetylcholine receptor antibody\u2010positive, non\u2010thymoma patients with generalized LOMG. All patients were of Italian ancestry. HLA\u2010DRB1 and \u2010DQB1 genotyping and serum titin antibody testing were performed in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 107 patients (females: 28\/107, 26.2%; median age of onset: 68\u00a0years, range: 50\u201092) were included. We found a positive association with HLA\u2010DRB1*07 (<jats:italic>P<\/jats:italic>\u00a0=\u00a01.1\u00a0\u00d7\u00a010<jats:sup>\u20105<\/jats:sup>), HLA\u2010DRB1*14 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0251) and HLA\u2010DQB1*02 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0095). HLA\u2010DRB1*03, HLA\u2010DRB1*11, and HLA\u2010DQB1*03 were protective alleles (<jats:italic>P<\/jats:italic>\u00a0=\u00a07.9\u00a0\u00d7\u00a010<jats:sup>\u20105<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0104, and <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0067, respectively). By conditional haplotype analysis, HLA\u2010DRB1*07\u2010DQB1*02 was found to be the major risk haplotype (OR\u00a0=\u00a04.10; 95% C.I.: 2.80\u20105.99; <jats:italic>P<\/jats:italic>\u00a0=\u00a06.01\u00a0\u00d7\u00a010<jats:sup>\u201011<\/jats:sup>). The mean age at onset was 73.4\u00a0years in DRB1*07 homozygotes, 69.7\u00a0years in heterozygotes, and 66.6 in non\u2010carriers (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0488). DRB1*07 carriers and non\u2010carriers did not differ in disease severity and response to therapy. Titin antibodies were detected in 61.4% of the cases, having no association with HLA alleles or specific clinical characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>In our study, we identified the HLA DRB1*07\u2010DQB1*02 haplotype as a predisposing factor for the development of generalized LOMG in the Italian population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51309","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T17:48:02Z","timestamp":1612806482000},"page":"656-665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Human Leukocyte Antigen Class II associations in late\u2010onset Myasthenia Gravis"],"prefix":"10.1002","volume":"8","author":[{"given":"Gregorio","family":"Spagni","sequence":"first","affiliation":[{"name":"Dipartimento di Neuroscienze Sezione di Neurologia Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Todi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e chirurgia traslazionale Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Sezione di Patologia generale Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Monte","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze Sezione di Neurologia Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Valentini","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e chirurgia traslazionale Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Sezione di Patologia generale Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Di Sante","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e chirurgia traslazionale Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Sezione di Patologia generale Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Damato","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze Sezione di Neurologia Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Rome Italy"},{"name":"U.O.C. di Neurologia Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariapaola","family":"Marino","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e chirurgia traslazionale Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Sezione di Patologia generale Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4644-2299","authenticated-orcid":false,"given":"Amelia","family":"Evoli","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze Sezione di Neurologia Universit\u00e0 Cattolica del Sacro Cuore Fondazione Policlinico Universitario \u201cA. Gemelli\u201d IRCCS Rome Italy"},{"name":"U.O.C. di Neurologia Fondazione Policlinico Universitario \u201cA. 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