{"title":"1型和2型嗜睡症患者的高分辨率HLA测序和下视素受体2自身抗体。","authors":"Samia Hamdan, Pontus Wasling, Alexander Lind","doi":"10.1111/iji.12688","DOIUrl":null,"url":null,"abstract":"<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-six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High-resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA-<i>DRB3</i>, <i>-DRB4</i>, <i>-DRB5</i>, <i>-DRB1</i>, <i>-DQA1</i>, <i>-DQB1</i>, <i>-DPA1</i>, and <i>-DPB1</i>. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti-HCRTR2 autoantibodies). NT1 was associated with <i>HLA-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i>, <i>-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i> (odds ratio [OR]: 9.15; <i>p</i> = 8.31 × 10<sup>−4</sup>) and <i>HLA-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i>, <i>-DRB4*01:03:01</i>, <i>-DRB1*04:01:01</i>, <i>-DQA1*03:02//03:03:01</i>, <i>-DQB1*03:01:01</i> (OR: 23.61; <i>p</i> = 1.58 × 10<sup>−4</sup>) genotypes. Lower orexin/hypocretin levels were reported in the NT2 subgroup (<i>n</i> = 5) that was associated with the extended <i>HLA-DQB1*06:02:01</i> haplotype (<i>p</i> = .001). Anti-HCRTR2 autoantibody levels were not different between study groups (<i>p</i> = .8524). We confirmed the previous association of NT1 with <i>HLA-DQB1*06:02:01</i> extended genotypes. A subgroup of NT2 patients with intermediate orexin/hypocretin levels and association with <i>HLA-DQB1*06:02:01</i> was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti-HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.</p>","PeriodicalId":14003,"journal":{"name":"International Journal of Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.3000,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12688","citationCount":"0","resultStr":"{\"title\":\"High-resolution HLA sequencing and hypocretin receptor 2 autoantibodies in narcolepsy type 1 and type 2\",\"authors\":\"Samia Hamdan, Pontus Wasling, Alexander Lind\",\"doi\":\"10.1111/iji.12688\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<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-six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High-resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA-<i>DRB3</i>, <i>-DRB4</i>, <i>-DRB5</i>, <i>-DRB1</i>, <i>-DQA1</i>, <i>-DQB1</i>, <i>-DPA1</i>, and <i>-DPB1</i>. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti-HCRTR2 autoantibodies). NT1 was associated with <i>HLA-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i>, <i>-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i> (odds ratio [OR]: 9.15; <i>p</i> = 8.31 × 10<sup>−4</sup>) and <i>HLA-DRB5*01:01:01</i>, <i>-DRB1*15:01:01</i>, <i>-DQA1*01:02:01</i>, <i>-DQB1*06:02:01</i>, <i>-DRB4*01:03:01</i>, <i>-DRB1*04:01:01</i>, <i>-DQA1*03:02//03:03:01</i>, <i>-DQB1*03:01:01</i> (OR: 23.61; <i>p</i> = 1.58 × 10<sup>−4</sup>) genotypes. Lower orexin/hypocretin levels were reported in the NT2 subgroup (<i>n</i> = 5) that was associated with the extended <i>HLA-DQB1*06:02:01</i> haplotype (<i>p</i> = .001). Anti-HCRTR2 autoantibody levels were not different between study groups (<i>p</i> = .8524). We confirmed the previous association of NT1 with <i>HLA-DQB1*06:02:01</i> extended genotypes. A subgroup of NT2 patients with intermediate orexin/hypocretin levels and association with <i>HLA-DQB1*06:02:01</i> was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti-HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.</p>\",\"PeriodicalId\":14003,\"journal\":{\"name\":\"International Journal of Immunogenetics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iji.12688\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Immunogenetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/iji.12688\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Immunogenetics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/iji.12688","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
High-resolution HLA sequencing and hypocretin receptor 2 autoantibodies in narcolepsy type 1 and type 2
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-six NT1 and 15 NT2 patients were included, together with control groups of 24 idiopathic hypersomnia (IH) patients and 778 general population participants. High-resolution sequencing was used to determine the alleles, the extended haplotypes, and the genotypes of HLA-DRB3, -DRB4, -DRB5, -DRB1, -DQA1, -DQB1, -DPA1, and -DPB1. Radiobinding assay was used to determine autoantibodies against hypocretin receptor 2 (anti-HCRTR2 autoantibodies). NT1 was associated with HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01 (odds ratio [OR]: 9.15; p = 8.31 × 10−4) and HLA-DRB5*01:01:01, -DRB1*15:01:01, -DQA1*01:02:01, -DQB1*06:02:01, -DRB4*01:03:01, -DRB1*04:01:01, -DQA1*03:02//03:03:01, -DQB1*03:01:01 (OR: 23.61; p = 1.58 × 10−4) genotypes. Lower orexin/hypocretin levels were reported in the NT2 subgroup (n = 5) that was associated with the extended HLA-DQB1*06:02:01 haplotype (p = .001). Anti-HCRTR2 autoantibody levels were not different between study groups (p = .8524). We confirmed the previous association of NT1 with HLA-DQB1*06:02:01 extended genotypes. A subgroup of NT2 patients with intermediate orexin/hypocretin levels and association with HLA-DQB1*06:02:01 was identified, indicating a possible overlap between the two distinct narcolepsy subtypes, NT1 and NT2. Low anti-HCRTR2 autoantibody levels suggest that these receptors might not function as autoimmune targets in either NT1 or NT2.
期刊介绍：
The International Journal of Immunogenetics (formerly European Journal of Immunogenetics) publishes original contributions on the genetic control of components of the immune system and their interactions in both humans and experimental animals. The term ''genetic'' is taken in its broadest sense to include studies at the evolutionary, molecular, chromosomal functional and population levels in both health and disease. Examples are:
-studies of blood groups and other surface antigens-
cell interactions and immune response-
receptors, antibodies, complement components and cytokines-
polymorphism-
evolution of the organisation, control and function of immune system components-
anthropology and disease associations-
the genetics of immune-related disease: allergy, autoimmunity, immunodeficiency and other immune pathologies-
All papers are seen by at least two independent referees and only papers of the highest quality are accepted.
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