{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:46:48Z","timestamp":1788389208602,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007373","name":"Stiftelsen Sven Jerrings Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018850","name":"Gunvor och Josef An\u00e9rs Siftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008594","name":"Linn\u00e9a och Josef Carlssons Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008352","name":"Stiftelsen Samariten","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009738","name":"Anna och Edwin Bergers Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005390","name":"Alfred \u00d6sterlunds Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005390","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006285","name":"Magnus Bergvalls Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006285","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003173","name":"Crafoordska Stiftelsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003173","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003186","name":"Fredrik och Ingrid Thurings Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003186","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007687","name":"Svenska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunogenetics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Narcolepsy is a sleep disorder caused by an apparent degeneration of orexin\/hypocretin neurons in the lateral hypothalamic area and a subsequent decrease in orexin\/hypocretin levels in the cerebrospinal fluid. Narcolepsy is classified into type 1 (NT1) and type 2 (NT2). While genetic associations in the human leukocyte antigen (HLA) region and candidate autoantibodies have been investigated in NT1 to imply an autoimmune origin, less is known about the pathogenesis in NT2. Twenty\u2010six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High\u2010resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA\u2010<jats:italic>DRB3<\/jats:italic>, <jats:italic>\u2010DRB4<\/jats:italic>, <jats:italic>\u2010DRB5<\/jats:italic>, <jats:italic>\u2010DRB1<\/jats:italic>, <jats:italic>\u2010DQA1<\/jats:italic>, <jats:italic>\u2010DQB1<\/jats:italic>, <jats:italic>\u2010DPA1<\/jats:italic>, and <jats:italic>\u2010DPB1<\/jats:italic>. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti\u2010HCRTR2 autoantibodies). NT1 was associated with <jats:italic>HLA\u2010DRB5*01:01:01<\/jats:italic>, <jats:italic>\u2010DRB1*15:01:01<\/jats:italic>, <jats:italic>\u2010DQA1*01:02:01<\/jats:italic>, <jats:italic>\u2010DQB1*06:02:01<\/jats:italic>, <jats:italic>\u2010DRB5*01:01:01<\/jats:italic>, <jats:italic>\u2010DRB1*15:01:01<\/jats:italic>, <jats:italic>\u2010DQA1*01:02:01<\/jats:italic>, <jats:italic>\u2010DQB1*06:02:01<\/jats:italic> (odds ratio [OR]: 9.15; <jats:italic>p<\/jats:italic>\u00a0=\u00a08.31\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>) and <jats:italic>HLA\u2010DRB5*01:01:01<\/jats:italic>, <jats:italic>\u2010DRB1*15:01:01<\/jats:italic>, <jats:italic>\u2010DQA1*01:02:01<\/jats:italic>, <jats:italic>\u2010DQB1*06:02:01<\/jats:italic>, <jats:italic>\u2010DRB4*01:03:01<\/jats:italic>, <jats:italic>\u2010DRB1*04:01:01<\/jats:italic>, <jats:italic>\u2010DQA1*03:02\/\/03:03:01<\/jats:italic>, <jats:italic>\u2010DQB1*03:01:01<\/jats:italic> (OR: 23.61; <jats:italic>p<\/jats:italic>\u00a0=\u00a01.58\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>) genotypes. Lower orexin\/hypocretin levels were reported in the NT2 subgroup (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) that was associated with the extended <jats:italic>HLA\u2010DQB1*06:02:01<\/jats:italic> haplotype (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.001). Anti\u2010HCRTR2 autoantibody levels were not different between study groups (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.8524). We confirmed the previous association of NT1 with <jats:italic>HLA\u2010DQB1*06:02:01<\/jats:italic> extended genotypes. A subgroup of NT2 patients with intermediate orexin\/hypocretin levels and association with <jats:italic>HLA\u2010DQB1*06:02:01<\/jats:italic> was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti\u2010HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.<\/jats:p>","DOI":"10.1111\/iji.12688","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T04:53:06Z","timestamp":1718859186000},"page":"310-318","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High\u2010resolution HLA sequencing and hypocretin receptor 2 autoantibodies in narcolepsy type 1 and type 2"],"prefix":"10.1111","volume":"51","author":[{"given":"Samia","family":"Hamdan","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Malm\u00f6 Lund University  Malmo Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus","family":"Wasling","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neuroscience and Physiology Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Neurology Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1473-5468","authenticated-orcid":false,"given":"Alexander","family":"Lind","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Malm\u00f6 Lund University  Malmo Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aab2354"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.13065"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2080"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/32.8.979"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13203"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2018.08.024"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.12.1667"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsw056"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23799"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22587"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2006.10.006"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000005346"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.100"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100540\u20101"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010023\u201000902\u20109"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165\u20105728(01)00333\u20102"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0222882"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2022.113265"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818150116"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187305"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2205797119"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.10748"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.10.1553"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1086\/318799"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(05)78496\u20108"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41439\u2010018\u20100033\u20107"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu480"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2015.31"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071376"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2015.05.001"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(99)05582\u20108"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.12.010"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673\u20105374.280322"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(14)70075\u20104"},{"issue":"4","key":"e_1_2_8_36_1","first-page":"541","article-title":"Relative predispositional effects (RPEs) of marker alleles with disease: HLA\u2010DR alleles and Graves disease","volume":"45","author":"Payami H.","year":"1989","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201008774\u20101"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.13665"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsw070"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.6882"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910\u2010018\u20100851\u20105"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14\u20100970"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2014.08.206"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.3300"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(00)00058\u20101"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/32.8.993"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.2922"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11325\u2010021\u201002525\u20107"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsac052"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005\u2010016\u20100435\u20105"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2019.1643843"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/wnp.0000000000000688"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2022.101610"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15\u20101115"}],"container-title":["International Journal of Immunogenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iji.12688","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T04:20:16Z","timestamp":1731730816000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iji.12688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,19]]},"references-count":53,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1111\/iji.12688"],"URL":"https:\/\/doi.org\/10.1111\/iji.12688","archive":["Portico"],"relation":{},"ISSN":["1744-3121","1744-313X"],"issn-type":[{"value":"1744-3121","type":"print"},{"value":"1744-313X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,19]]},"assertion":[{"value":"2024-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}